Umeå University's logo

umu.sePublications
Change search
Refine search result
12 1 - 50 of 83
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Alonso-Magdalena, Lucía
    et al.
    Zia, Elisabet
    Carmona I Codina, Olga
    Pessah-Rasmussen, Hélène
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Incidence and prevalence of multiple sclerosis in Malmö, southern Sweden2022In: Multiple Sclerosis International, ISSN 2090-2654, E-ISSN 2090-2662, article id 5464370Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To estimate the incidence and prevalence of multiple sclerosis (MS) in Malmö municipality in southwestern Sweden.

    MATERIALS AND METHODS: Multiple sources were used in the case identification process. Case ascertainment was assessed by medical chart review including examinations such as magnetic resonance imaging, cerebrospinal fluid analyses, and relevant laboratory tests. Cases were classified according to the 2010 McDonald's diagnostic criteria. Onset-adjusted prevalence and a definition of onset symptoms were applied.

    RESULTS: The crude incidence of MS in 2001-2010 in Malmö municipality was 5.3/100,000 (95% confidence interval (CI): 4.5 to 6.2). There was a relapsing onset in 90.5% of cases. The female to male ratio was 1.8. The onset-adjusted prevalence for Dec 2010 was 133/100,000 (95% CI, 120 to 146) with a female to male ratio of 2.1.

    CONCLUSIONS: This is the first population-based epidemiological study in Skåne, the most southwestern part of Sweden showing a high incidence and prevalence. We found a lower incidence than expected according to previous nationwide figures, probably due to methodological differences between the studies. Our findings support the presence of a north-south gradient of MS prevalence in Sweden.

    Download full text (pdf)
    fulltext
  • 2. Axelsson, Markus
    et al.
    Malmeström, Clas
    Gunnarsson, Martin
    Zetterberg, Henrik
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lycke, Jan
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2013In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 11, Supplement: S, p. 543-543Article in journal (Other academic)
  • 3. Axelsson, Markus
    et al.
    Malmeström, Clas
    Gunnarsson, Martin
    Zetterberg, Henrik
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lycke, Jan
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2014In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 1, p. 43-50Article in journal (Refereed)
    Abstract [en]

    Background: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. Objective: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). Methods: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. Results: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. Conclusions: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.

  • 4.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Alonso-Magdalena, Lucia
    Andersen, Oluf
    Jons, Daniel
    Gunnarsson, Martin
    Vrethem, Magnus
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    High serum concentration of vitamin D may protect against multiple sclerosis2019In: Multiple Sclerosis Journal, Experimental, Translational and Clinical, E-ISSN 2055-2173, Vol. 5, no 4Article in journal (Refereed)
    Abstract [en]

    Background: High 25-hydroxyvitamin D concentrations have been associated with a reduced risk of multiple sclerosis, with indications of a stronger effect among young individuals.

    Objective: Investigate the 25-hydroxyvitamin D association with multiple sclerosis and test if this association is age dependent.

    Methods: Prospectively drawn blood samples from individuals later developing relapsing-remitting multiple sclerosis and controls matched for biobank, sex, age and date of sampling, were analysed with liquid chromatography tandem mass spectrometry.

    Results: High levels of 25-hydroxyvitamin D (top quintile) were associated with a reduced multiple sclerosis risk (odds ratio 0.68, 95% confidence interval 0.50-0.93).

    Conclusion: These findings further support a role for vitamin D in MS aetiology.

    Download full text (pdf)
    fulltext
  • 5.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gustafsson, R.
    Engdahl, E.
    Bomfim, I. L.
    Huang, J.
    Jons, D.
    Andersen, O.
    Hortlund, M.
    Alonso-Magdalena, L.
    Waterboer, T.
    Kockum, I.
    Olsson, T.
    Fogdell-Hahn, A.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Late Epstein-Barr virus infection and a second virus are linked to multiple sclerosis risk2016In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 187-187Article in journal (Refereed)
  • 6.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Andersen, O.
    Alonso-Magdalena, L.
    Jons, D.
    Gunnarsson, M.
    Vrethem, M.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Leptin levels are associated with multiple sclerosis risk2019In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 904-904Article in journal (Other academic)
  • 7.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Andersen, Oluf
    Alonso-Magdalena, Lucia
    Jons, Daniel
    Gunnarsson, Martin
    Vrethem, Magnus
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Leptin levels are associated with multiple sclerosis risk2021In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, no 1, p. 19-27Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity early in life has been linked to increased risk of developing multiple sclerosis (MS). Leptin and insulin are both associated with obesity, making them suitable candidates for investigating this connection.

    OBJECTIVE: To determine if leptin and insulin are risk factors for relapsing-remitting multiple sclerosis (RRMS).

    METHODS: In this nested case-control study using blood samples from Swedish biobanks, we compared concentrations of leptin and insulin in 649 individuals who later developed RRMS with 649 controls matched for biobank, sex, age and date of sampling. Only pre-symptomatically drawn samples from individuals below the age of 40 years were included. Conditional logistic regression was performed on z-scored values to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

    RESULTS: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals younger than 20 years (OR = 1.4, 95% CI = 1.1-1.9) and in all men (OR = 1.4, 95% CI = 1.0-2.0). In contrast, for women aged 30-39 years, there was a lower risk of MS with increased leptin levels (OR = 0.74, 95% CI = 0.54-1.0) when adjusting for insulin levels.

    CONCLUSION: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals.

    Download full text (pdf)
    fulltext
  • 8.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Response to 'Mendelian randomization analysis does not support a role for leptin in multiple sclerosis'2021In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, no 1, p. 161-162Article in journal (Refereed)
  • 9.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Jons, Daniel
    Engdahl, Elin
    Gustafsson, Rasmus
    Huang, Jesse
    Brenner, Nicole
    Butt, Julia
    Alonso-Magdalena, Lucia
    Gunnarsson, Martin
    Vrethem, Magnus
    Bender, Noemi
    Waterboer, Tim
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olsson, Tomas
    Kockum, Ingrid
    Andersen, Oluf
    Fogdell-Hahn, Anna
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Epstein-Barr virus infection after adolescence and Human herpesvirus 6A as risk factors for multiple sclerosis2021In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 28, no 2, p. 579-586Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Infections with human herpesvirus 6A (HHV‐6A) and Epstein–Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV‐6A associated risks of developing MS.

    Methods:  In this nested case–control study, Swedish biobanks were accessed to find pre‐symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead‐based multiplex assay was used to determine serological response against EBV and HHV‐6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.

    Results: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20–29 and 30–39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV‐6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6–2.7).

    Conclusions: This study suggests EBV infection after adolescence and age independent HHV‐6A infection as risk factors for MS.

    Download full text (pdf)
    fulltext
  • 10.
    Boremalm, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Discontinuation and dose reduction of rituximab in relapsing-remitting multiple sclerosis2021In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 268, no 6, p. 2161-2168Article in journal (Refereed)
    Abstract [en]

    Background: Rituximab is safe and effective for treating relapsing–remitting multiple sclerosis (RRMS) according to phase II and observational studies. There are limited data on disease activity after discontinuation and dose reduction. The objective of this study was to evaluate the effects on inflammatory disease activity after discontinuation or dose reduction of rituximab in patients with RRMS or clinically isolated syndrome (CIS).

    Methods: In this retrospective observational study, we included all RRMS and CIS patients ever treated with rituximab at the University Hospital of Umeå who had either; (1) discontinued treatment at any time or (2) reduced the dose to a mean of < 1000 mg yearly. The patients served as their own controls by contributing patient years on full dose, reduced dose, and off treatment.

    Results: A total of 225 patients treated with mean (SD) 6256 (2456) mg rituximab during mean (SD) 6.5 (2.0) years were included. There were no differences regarding the annualized relapse rates during full dose versus reduced dose or off treatment (0.02 versus < 0.01 and 0.02, p = 0.09), neither regarding proportion MRI scans with new or enlarged T2 lesions (0.03 versus 0.01 and 0.03, p = 0.37) or contrast-enhancing lesions (< 0.01 versus 0 and 0.02, p = 0.22).

    Conclusions: This study indicates that rituximab has long-term effects on inflammatory disease activity and that disease reactivation is rare in MS patients who discontinued treatment for any reason. It also suggests that treatment with low-dose rituximab (< 1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity in patients with stable disease.

    Download full text (pdf)
    fulltext
  • 11.
    de Flon, Pierre
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gunnarsson, Martin
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Krauss, Wolfgang
    Dring, Ann
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bergman, Joakim
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab2016In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, no 2, p. 141-147Article in journal (Refereed)
    Abstract [en]

    Objective: To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS).

    Method: Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study. After a run-in period of 3 months, 2 IV doses of 1,000 mg rituximab were given 2 weeks apart followed by repeated clinical assessment, MRI, and CSF-NFL for 24 months.

    Results: The mean cumulated number of gadolinium-enhancing lesions per patient at months 3 and 6 after treatment shift to rituximab was reduced compared to the run-in period (0.028 vs 0.36, p = 0.029). During the first year after treatment shift, the mean number of new or enlarged T2 lesions per patient was reduced (0.01 vs 0.28, p = 0.004) and mean CSF-NFL levels were reduced by 21% (p = 0.01).

    Conclusions: For patients with RRMS, a treatment switch from IFN or GA to rituximab is associated with reduced inflammatory activity measured by MRI and CSF-NFL.

    Classification of evidence: This study provides Class IV evidence that rituximab has an equal or superior effect in reducing inflammatory activity in RRMS measured by MRI and CSF-NFL compared to first-line injectables during the first year after treatment shift.

  • 12.
    de Flon, Pierre
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blennow, Kaj
    Söderström, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Zetterberg, Henrik
    Gunnarsson, Martin
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Karolinska Institute Danderyd Hospital, Stockholm, Sweden.
    Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 5, p. 462-468Article in journal (Refereed)
    Abstract [en]

    Objective: The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis.

    Materials and methods: Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed up for 2 years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed up for an additional 3 years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA.

    Results: The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 [SD 393] to 354 [SD 174] pg/mL; P = 0.006) and was statistically significant. The corresponding reduction in plasma NFL was 18% (from 9.73 [SD 7.04] to 7.94 [SD 3.10] pg/mL; P = 0.055) and did not reach statistical significance.

    Conclusion: This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimize the use in clinical trials.

  • 13.
    de Flon, Pierre
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dring, Ann
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gunnarsson, Martin
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Dept of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm.
    Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192516Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate changes in the cerebrospinal fluid (CSF) immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS), and to compare the profile in MS patients with healthy controls (HC).

    METHOD: Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.

    RESULTS: Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10), IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8) decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.

    CONCLUSION: We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

    Download full text (pdf)
    fulltext
  • 14. Engdahl, Elin
    et al.
    Gustafsson, Rasmus
    Huang, Jesse
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Lima Bomfim, Izaura
    Stridh, Pernilla
    Khademi, Mohsen
    Brenner, Nicole
    Butt, Julia
    Michel, Angelika
    Jons, Daniel
    Hortlund, Maria
    Alonso-Magdalena, Lucia
    Hedström, Anna Karin
    Flamand, Louis
    Ihira, Masaru
    Yoshikawa, Tetsushi
    Andersen, Oluf
    Hillert, Jan
    Alfredsson, Lars
    Waterboer, Tim
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Olsson, Tomas
    Kockum, Ingrid
    Fogdell-Hahn, Anna
    Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis2019In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 10, article id 2715Article in journal (Refereed)
    Abstract [en]

    Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.

    Download full text (pdf)
    fulltext
  • 15. Forsberg, L.
    et al.
    Kågström, S.
    Fält, A.
    Berglund, A.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Svenningsson, A.
    Lycke, J.
    Landtblom, A. -M
    Burman, J.
    Martin, C.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gunnarsson, M.
    Piehl, F.
    Olsson, T.
    Clinical effectiveness of dimethyl fumarate with focus on patients treated at least 36 months - a Swedish nationwide study of the long-term effectiveness and safety of dimethyl fumarate (IMSE5)2019In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 316-317Article in journal (Other academic)
  • 16. Forsberg, L.
    et al.
    Kågström, S.
    Fält, A.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Svenningsson, A.
    Lycke, J.
    Landtblom, A. -M
    Burman, J.
    Martin, C.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gunnarsson, M.
    Piehl, F.
    Olsson, T.
    A Swedish Nationwide study of the long-term effectiveness and safety of teriflunomid based on data from the Swedish "Immunomodulation and Multiple Sclerosis Epidemiology" Study (IMSE 4)2019In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 316-316Article in journal (Other academic)
  • 17. Fält, A.
    et al.
    Kågström, S.
    Forsberg, L.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Svenningsson, A.
    Lycke, J.
    Landtblom, A. -M
    Burman, J.
    Martin, C.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gunnarsson, M.
    Piehl, F.
    Olsson, T.
    A swedish post-market surveillance study of the long-term effectiveness and safety of alemtuzumab (IMSE 3) for patients treated at least 24 months2019In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 327-328Article in journal (Other academic)
  • 18. Fält, A.
    et al.
    Kågström, S.
    Forsberg, L.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Svenningsson, A.
    Lycke, J.
    Landtblom, A. -M
    Burman, J.
    Martin, C.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gunnarsson, M.
    Piehl, F.
    Olsson, T.
    A Swedish real word study of the long-term effectiveness and safety of fingolimod (IMSE 2) with focus on patients treated at least 48 months2019In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 536-537Article in journal (Other academic)
  • 19. Granqvist, Mathias
    et al.
    Burman, Joachim
    Gunnarsson, Martin
    Lycke, Jan
    Nilsson, Petra
    Olsson, Tomas
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Svenningsson, Anders
    Vrethem, Magnus
    Frisell, Thomas
    Piehl, Fredrik
    Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS2020In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, no 12, p. 1532-1539Article in journal (Refereed)
    Abstract [en]

    Background: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited. Objective: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden. Methods: We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF (n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF (n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016. Results: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58, p < 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09, p < 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13; p < 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04; p = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy (p < 0.05 and p = 0.20, respectively). Conclusion: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.

  • 20.
    Grut, Viktor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stridh, Pernilla
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Jons, Daniel
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gustafsson, Rasmus
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Fogdell-Hahn, Anna
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Huang, Jesse
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Brenner, Nicole
    Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Butt, Julia
    Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Bender, Noemi
    Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Lindam, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine. Unit of Research, Education and Development Östersund Hospital, Umeå University, Umeå, Sweden.
    Alonso-Magdalena, Lucia
    Department of Neurology, Skåne University Hospital in Malmö/Lund and Institution of Clinical Sciences, Neurology, Lund University, Lund, Sweden.
    Gunnarsson, Martin
    Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Vrethem, Magnus
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Bergström, Tomas
    Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Andersen, Oluf
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Kockum, Ingrid
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Waterboer, Tim
    Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Olsson, Tomas
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis: a presymptomatic case–control study2021In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 28, no 9, p. 3072-3079Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Epstein–Barr virus (EBV) and human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, it was sought to increase the understanding of CMV in MS aetiology.

    Methods: A nested case–control study was performed with presymptomatically collected blood samples identified through crosslinkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95% confidence interval (CI) for CMV seropositivity as a risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating the attributable proportion due to interaction (AP).

    Results: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56–0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06–0.61) and EBV antigen EBNA-1 (amino acid 385–420) at age 20–39 years (AP 0.37, 95% CI 0.09–0.65).

    Conclusions: Cytomegalovirus seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.

    Download full text (pdf)
    fulltext
  • 21.
    Grut, Viktor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stridh, Pernilla
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Jons, Daniel
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gustafsson, Rasmus
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Fogdell-Hahn, Anna
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Huang, Jesse
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Butt, Julia
    Infections and Cancer Epidemiology Division, German Cancer Research Center, Heidelberg, Germany.
    Lindam, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Alonso-Magdalena, Lucia
    Department of Neurology, Skåne University Hospital and Department of Clinical Sciences, Lund University, Lund, Sweden.
    Bergström, Tomas
    Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Kockum, Ingrid
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Waterboer, Tim
    Infections and Cancer Epidemiology Division, German Cancer Research Center, Heidelberg, Germany.
    Olsson, Tomas
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, Ucl Institute of Neurology, London, United Kingdom; Uk Dementia Research Institute at Ucl, London, United Kingdom; Hong Kong Centre for Neurodegenerative Diseases, Hong Kong, Hong Kong; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, Madison, United States.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Andersen, Oluf
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Staffan
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis2024In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 147, no 1, p. 177-185Article in journal (Refereed)
    Abstract [en]

    Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A.

    A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI).

    Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis).

    In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.

    Download full text (pdf)
    fulltext
  • 22.
    Grut, Viktor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stridh, Pernilla
    Lindam, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine. Unit of Research, Education, and Development, Östersund Hospital, Umeå University, Umeå, Sweden.
    Alonso-Magdalena, Lucia
    Andersen, Oluf
    Jons, Daniel
    Gunnarsson, Martin
    Vrethem, Magnus
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Free vitamin D3 index and vitamin D-binding protein in multiple sclerosis: A presymptomatic case-control study2022In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 29, no 8, p. 2335-2342Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: High levels of 25-hydroxyvitamin D3 (25[OH]D3 ) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS.

    METHODS: A nested case-control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3 /DBP) × 103 . MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs).

    RESULTS: Serum samples from 660 pairs of matched cases and controls were included. At <20 years of age, high levels of free vitamin D3 index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15-0.91, p for trend across quintiles = 0.04). At age 30-39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15-0.85, p for trend = 0.02).

    CONCLUSIONS: These findings support the hypothesis that high levels of free 25(OH)D3 at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.

    Download full text (pdf)
    fulltext
  • 23.
    Grut, Viktor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stridh, Pernilla
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Lindam, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Alonso-Magdalena, Lucia
    Department of Neurology, Skåne University Hospital and Department of Clinical Sciences, Neurology, Lund University, Lund, Sweden.
    Andersen, Oluf
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Jons, Daniel
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gunnarsson, Martin
    Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Vrethem, Magnus
    Department of Neurology and Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Systemic inflammation and risk of multiple sclerosis: a presymptomatic case-control study2022In: Multiple Sclerosis Journal, Experimental, Translational and Clinical, E-ISSN 2055-2173, Vol. 8, no 4, p. 1-4Article in journal (Refereed)
    Abstract [en]

    Background: C-reactive protein (CRP) is a marker of systemic inflammation. Increased levels of CRP in young persons have been suggested to decrease the risk of multiple sclerosis (MS).

    Objectives: To assess CRP as a risk factor for MS.

    Methods: Levels of CRP were measured with a high-sensitive immunoassay in biobank samples from 837 individuals who later developed MS and 984 matched controls. The risk of developing MS was analysed by conditional logistic regression on z-scored CRP values.

    Results: Levels of CRP were not associated with MS risk.

    Conclusions: We found no association between CRP levels and risk of MS development.

    Download full text (pdf)
    fulltext
  • 24.
    Gröning, Remigius
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Dernstedt, Andy
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis patients after rituximab treatment interruption2023In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1219560Article in journal (Refereed)
    Abstract [en]

    Peripheral B cell depletion via anti-CD20 treatment is a highly effective disease-modifying treatment for reducing new relapses in multiple sclerosis (MS) patients. A drawback of rituximab (RTX) and other anti-CD20 antibodies is a poor immune response to vaccination. While this can be mitigated by treatment interruption of at least six months prior to vaccination, the timing to resume treatment while maintaining subsequent vaccine responses remains undetermined. Here, we characterized SARS-CoV-2 S-directed antibody and B cell responses throughout three BNT162b2 mRNA vaccine doses in RTX-treated MS patients, with the first two doses given during treatment interruption. We examined B-cell mediated immune responses in blood samples from patients with RTX-treated MS throughout three BNT162b2 vaccine doses, compared to an age- and sex-matched healthy control group. The first vaccine dose was given 1.3 years (median) after the last RTX infusion, the second dose one month after the first, and the third dose four weeks after treatment re-initiation. We analyzed SARS-CoV-2 S-directed antibody levels using enzyme-linked immunosorbent assay (ELISA), and the neutralization capacity of patient serum against SARS-CoV-2 S-pseudotyped lentivirus using luciferase reporter assay. In addition, we assessed switched memory (CD19+CD20+CD27+IgD-), unswitched memory (CD19+CD20+CD27+IgD+), naïve (CD19+CD20+CD27-IgD+), and double negative (DN, CD19+CD20+CD27-IgD-) B cell frequencies, as well as their SARS-CoV-2 S-specific (CoV+) and Decay Accelerating Factor-negative (DAF-) subpopulations, using flow cytometry. After two vaccine doses, S-binding antibody levels and neutralization capacity in SARS-CoV-2-naïve MS patients were comparable to vaccinated healthy controls, albeit with greater variation. Higher antibody response levels and CoV+-DN B cell frequencies after the second vaccine dose were predictive of a boost effect after the third dose, even after re-initiation of rituximab treatment. MS patients also exhibited lower frequencies of DAF- memory B cells, a suggested proxy for germinal centre activity, than control individuals. S-binding antibody levels in RTX-treated MS patients after two vaccine doses could help determine which individuals would need to move up their next vaccine booster dose or postpone their next RTX infusion. Our findings also offer first indications on the potential importance of antigenic stimulation of DN B cells and long-term impairment of germinal centre activity in rituximab-treated MS patients.

    Download full text (pdf)
    fulltext
  • 25.
    Gröning, Remigius
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Dernstedt, Andy
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Gardfjäll, Jenny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Variable immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis after rituximab treatment interruptionManuscript (preprint) (Other academic)
  • 26. Gunnarsson, Martin
    et al.
    Malmeström, Clas
    Axelsson, Markus
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Dahle, Charlotte
    Vrethem, Magnus
    Olsson, Tomas
    Piehl, Fredrik
    Norgren, Niklas
    Rosengren, Lars
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lycke, Jan
    Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab2011In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 69, no 1, p. 83-89Article in journal (Refereed)
    Abstract [en]

    Our data demonstrate that natalizumab treatment reduces the accumulation of nerve injury in relapsing forms of MS. It is anticipated that highly effective anti-inflammatory treatment can reduce axonal loss, thereby preventing development of permanent neurological disability.

  • 27. Hultin, Emilie
    et al.
    Arroyo Mühr, Laila Sara
    Bzhalava, Zurab
    Hortlund, Maria
    Lagheden, Camilla
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dillner, Joakim
    Viremia preceding multiple sclerosis: Two nested case-control studies2018In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 520, p. 21-29Article in journal (Refereed)
    Abstract [en]

    Infections have been suggested to be involved in Multiple Sclerosis (MS). We used metagenomic sequencing to detect both known and yet unknown microorganisms in 2 nested case control studies of MS. Two different cohorts were followed for MS using registry linkages. Serum samples taken before diagnosis as well as samples from matched control subjects were selected.

    In cohort1 with 75 cases and 75 controls, most viral reads were Anelloviridae-related and >95% detected among the cases. Among samples taken up to 2 years before MS diagnosis, Anellovirus species TTMV1, TTMV6 and TTV27 were significantly more common among cases. In cohort2, 93 cases and 93 controls were tested under the pre-specified hypothesis that the same association would be found. Although most viral reads were again related to Anelloviridae, no significant case-control differences were seen. We conclude that the Anelloviridae-MS association may be due to multiple hypothesis testing, but other explanations are possible.

  • 28. Jons, D
    et al.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersen, O
    Targeting Epstein-Barr virus infection as an intervention against multiple sclerosis2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 131, no 2, p. 69-79Article, review/survey (Refereed)
    Abstract [en]

    We here review contemporary data on genetic and environmental risk factors, particularly Epstein-Barr virus infection, for multiple sclerosis. There is an important immunogenetic etiological factor for multiple sclerosis. However, a general assumption is that immune defense genes are activated by the environment, basically by infections. We contend that the relationship between infectious mononucleosis and multiple sclerosis cannot be completely explained by genetics and inverse causality. Epstein-Barr infection as indicated by positive serology is an obligatory precondition for multiple sclerosis, which is a stronger attribute than a risk factor only. Data on events in the early pathogenesis of multiple sclerosis are cumulating from bio-banks with presymptomatic specimens, but there is only little information from the critical age when Epstein-Barr infection including infectious mononucleosis is acquired, nor on the detailed immunological consequences of this infection in individuals with and without multiple sclerosis. We discuss how focused bio-banking may elaborate a rationale for the development of treatment or vaccination against Epstein-Barr virus infection. A cohort in which intervention against Epstein-Barr infections was performed should be the object of neurological follow-up.

  • 29. Jons, D.
    et al.
    Zetterberg, H.
    Malmeström, C.
    Axelsson, M.
    Bergström, T.
    Blennow, K.
    Thulin, M.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersen, O.
    Pilot study of intrathecal immunoreactivity in healthy people with or without previous infectious mononucleosis2019In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 667-668Article in journal (Other academic)
  • 30.
    Jons, Daniel
    et al.
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Grut, Viktor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Bergström, Tomas
    Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Clinical Microbiology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Gunnarsson, Martin
    Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Vrethem, Magnus
    Department of Neurology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Brenner, Nicole
    Infections and Cancer Epidemiology Infection, Inflammation, Cancer Research Program, German Cancer Research Center, Heidelberg, Germany.
    Butt, Julia
    Infections and Cancer Epidemiology Infection, Inflammation, Cancer Research Program, German Cancer Research Center, Heidelberg, Germany.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Nilsson, Staffan
    Mathematical Sciences, Chalmers University of Technology, Göteborg, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Kockum, Ingrid
    Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Center, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Olsson, Tomas
    Department of Clinical Neuroscience, The Karolinska Neuroimmunology & Multiple Sclerosis Center, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Waterboer, Tim
    Infections and Cancer Epidemiology Infection, Inflammation, Cancer Research Program, German Cancer Research Center, Heidelberg, Germany.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Andersen, Oluf
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage2023In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, article id 331868Article in journal (Refereed)
    Abstract [en]

    Background: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens.

    Methods: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury.

    Results: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001). With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026).

    Conclusions: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.

    Download full text (pdf)
    fulltext
  • 31.
    Jons, Daniel
    et al.
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 11, 3tr, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Persson Berg, Linn
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, the Sahlgrenska Academy, Gothenburg, Sweden and Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Haghighi, Sara
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden and Department of Medical Specialists, Institute of Neurology, Motala Hospital, Motala, Sweden.
    Axelsson, Markus
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Thulin, Måns
    School of Mathematics and Maxwell Institute for Mathematical Sciences, University of Edinburgh, UK, United Kingdom.
    Bergström, Tomas
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, the Sahlgrenska Academy, Gothenburg, Sweden and Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Andersen, Oluf
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 11, 3tr, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis2021In: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 56, article id 103288Article in journal (Refereed)
    Abstract [en]

    Background: A two- to three-fold increase in the risk of multiple sclerosis (MS) after infectious mononucleosis (IM) has been observed in cohort and case control studies. However, this association has not been investigated prospectively from IM. It remains to be determined whether long-term immunospecific sequelae with features consistent with presymptomatic MS occur after IM.

     Methods: Sera were obtained from individuals with acute IM from 2003–2007 (n = 42) and from the same individuals at a follow-up (FU) study approximately 10 years after IM. These were assayed for antibodies against a variety of Epstein-Barr virus (EBV) antigens, including gp350, a novel recombinant glycoprotein from the EBV envelope. Similarly, single-protein antigens were used to assess measles and varicella-zoster reactivity (Ncore and varicella-zoster glycoprotein E [VZVgE]). The FU study also included cerebrospinal fluid (CSF) samples from 21 of these individuals to test for IgG antibodies against the same viral antigens. As controls, CSF and serum samples were obtained from 15 EBV-seropositive volunteers who denied a history of IM, and serum samples were obtained from 24 EBV-seropositive blood donors. Anti-gp350, anti-Ncore and anti-VZVgE IgG levels were also analysed in sera and CSF samples from 22 persons with MS.

     Results: The FU assays showed higher anti-gp350 IgG (p = 0.007, univariate) than among healthy controls, with no difference in serum anti-VCA or anti-EBNA1 IgG levels and no difference in anti-gp350 in the CSF samples. Anti-Ncore IgG and anti-VZVgE were higher in acute IM samples (p < 0.001 and p < 0.0001, respectively) than at FU, although anti-Ncore remained heightened in an age-adjusted analysis at FU (p = 0.014) compared to the control group. In the MS group, the serum anti-gp350 and anti-Ncore IgG levels were significantly higher than among the control group, but the anti-VZVgE levels were not. The CSF anti-gp350 and VZVgE levels were slightly higher among persons with MS than among the control group, whereas anti-Ncore IgG was markedly higher in persons with MS than in the control group.

    Conclusion: In the present study IM showed certain similarities with MS. Increased anti-gp350 reactivity persisted more than a decade after IM, reminiscent of the established increased anti-EBV reactivity in presymptomatic MS. Acute IM was associated with increased anti-measles and anti-VZV immunoreactivity, similar to the MRZ reaction in MS, with some evidence suggesting that this measles reactivity persisted after a decade.

    Download full text (pdf)
    fulltext
  • 32.
    Jons, Daniel
    et al.
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Dahlgren's Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom; Hong Kong Centre for Neurodegenerative Diseases, Hong Kong.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Alonso-Magdalena, Lucia
    Department of Neurology, Skåne University Hospital, Lund, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
    Gunnarsson, Martin
    Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Vrethem, Magnus
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Dahlgren's Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Nilsson, Staffan
    Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Andersen, Oluf
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Axonal injury in asymptomatic individuals preceding onset of multiple sclerosis2022In: Annals of Clinical and Translational Neurology, E-ISSN 2328-9503, Vol. 9, no 6, p. 882-887Article in journal (Refereed)
    Abstract [en]

    Axonal loss is the main cause of irreversible disability in multiple sclerosis (MS). Serum neurofilament light (sNfL) is a biomarker of axonal disintegration. In this nested case–control study, blood samples from 519 presymptomatic persons (age range 4–39 years) who later received an MS diagnosis showed higher sNfL concentrations than 519 matched controls (p < 0.0001), noticeable at least 10 years before clinical MS onset. Mean values for pre-MS and control groups were 9.6 pg/mL versus 7.4 pg/mL 0–5 years before onset, and 6.4 pg/mL versus 5.8 pg/mL 5–10 years before onset. These results support that axonal injury occurs early in MS pathogenesis.

    Download full text (pdf)
    fulltext
  • 33. Jons, Daniel
    et al.
    Zetterberg, Henrik
    Malmeström, Clas
    Bergström, Tomas
    Axelsson, Markus
    Blennow, Kaj
    Thulin, Måns
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Andersen, Oluf
    Intrathecal immunoreactivity in people with or without previous infectious mononucleosis2020In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 142, no 2, p. 161-168Article in journal (Refereed)
    Abstract [en]

    Objectives: The risk of developing multiple sclerosis (MS) increases (OR: 3.1) after infectious mononucleosis (IM). However, the nature of this link is obscure. We tested the hypothesis that IM might incur long-term sequelae, including low-key inflammatory activity, with characteristics of an MS endophenotype (or presymptomatic trait) and that assays of MS-relevant cyto-/chemokines in the cerebrospinal fluid (CSF) post-IM may show a trend in this direction.

    Materials and methods: We selected seven CSF cytokines (IL-1b, IL-6, YKL-40, TNF-alpha) or chemokines (IL-8, CCL2, IP-10), representing pro-inflammatory factors previously associated with MS. We assayed the CSF levels of these seven cyto-/chemokines in healthy individuals with a median follow-up time of 10 years after serologically confirmed IM (post-IM group, n = 22), and in healthy controls without a history of IM (n = 19). A group of MS patients (n = 23) were included as reference.

    Results: The CSF levels of IP-10, YKL-40, and CCL-2 were higher in the post-IM group than in our IM unexposed controls (P = .021, .049, .028). Seven of seven cyto-/chemokine assays showed a trend in the predicted direction (Pof binomial ratio = .008). However, this trend was non-significant in a multivariate test (P = .22). A power analysis indicated that similar studies including a larger cohort would be numerically realistic.

    Conclusions: These results do not reject the hypothesis that the established epidemiological association between IM and MS results from a stepwise inflammatory propagation from IM sequelae to an MS endophenotype (or presymptomatic trait) in a proportion of IM patients, pending confirmation with adequate power.

  • 34. Kågström, S.
    et al.
    Fält, A.
    Forsberg, L.
    Berglund, A.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Svenningsson, A.
    Lycke, J.
    Landtblom, A. -M
    Burman, J.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Martin, C.
    Gunnarsson, M.
    Piehl, F.
    Olsson, T.
    Improved clinical outcomes in patients treated with natalizumab for at least 8 years - real-world data from a Swedish national post-marketing surveillance study (IMSE 1)2019In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 763-764Article in journal (Other academic)
  • 35.
    Linden, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, Anders
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Inflammatory activity and vitamin D levels in an MS population treated with rituximab2019In: Multiple Sclerosis Journal, Experimental, Translational and Clinical, E-ISSN 2055-2173, Vol. 5, no 1, article id 2055217319826598Article in journal (Refereed)
    Abstract [en]

    Background: Most multiple sclerosis patients on disease-modifying treatment at Umeå University Hospital are treated with rituximab and the prevalence of vitamin D supplementation has increased over time. Follow-up studies of these off-label treatments are needed.

    Objective: To study inflammatory activity and adverse effects in rituximab-treated multiple sclerosis patients, and associations with 25-hydroxy-vitamin D levels.

    Methods: Retrospectively collected data on repeated estimates of relapses, disability, side effects, magnetic resonance imaging, laboratory measures including 25-hydroxy-vitamin D levels and self-perceived health.

    Results: In 272 multiple sclerosis patients with a mean follow-up of 43 months, we identified seven possible relapses during active rituximab treatment. On magnetic resonance imaging examination, new T2 lesions were seen in 1.3% (10 out of 792 scans), and 0.25% (two out of 785 scans) showed contrast enhancement. Adjusted 25-hydroxy-vitamin D levels in samples drawn close to all magnetic resonance images with new T2 lesions were lower compared to the remainder (62 vs. 81 nmol/l; P = 0.030). Levels of 25-hydroxy-vitamin D were associated with self-perceived health (r = 0.18, P = 0.041, n = 130) and C-reactive protein (r = -0.13, P = 0.042) but not with the risk of side effects.

    Conclusion: The inflammatory activity in this rituximab-treated multiple sclerosis population that increasingly used vitamin D supplementation was extremely low. Higher 25-hydroxy-vitamin D levels were associated with beneficial outcomes.

    Download full text (pdf)
    fulltext
  • 36.
    Norgren, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Rosengren, Lars
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Gunnarsson, Martin
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Neurofilament light and glial fibrillary acidic protein in multiple sclerosis2004In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 63, no 9, p. 1586-1590Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) in CSF from patients with multiple sclerosis (MS) in relation to clinical progress of the disease.

    Methods: CSF levels of NFL and GFAP were determined by sensitive ELISAs in 99 patients with different subtypes of MS, classified in terms of “ongoing relapse” or “clinically stable disease,” and 25 control subjects. Levels were compared with paraclinical data such as immunoglobulin G index and inflammatory cell count in the CSF, and the levels were related to Expanded Disability Status Scale score and progression index at clinical follow-up evaluations later in the disease course.

    Results: NFL and GFAP levels were elevated in MS patients as compared with control subjects (p < 0.001). The NFL levels were higher at relapses, whereas GFAP levels were unaffected. High NFL levels correlated with progression in patients with an active relapse (r = 0.49; p < 0.01) and in clinically stable patients (r = 0.29; p < 0.05). GFAP correlated to progression in the total patient cohort (r = 0.24; p < 0.05). Moreover, a strong correlation between NFL levels and inflammatory cell counts was evident in the group of patients with an ongoing relapse (r = 0.52; p = 0.001).

    Conclusions: CSF levels of neurofilament light and glial fibrillary acidic protein may have prognostic value in multiple sclerosis.

  • 37. Novakova, L.
    et al.
    Zetterberg, H.
    Axelsson, M.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Khademi, M.
    Gunnarsson, M.
    Malmestrom, C.
    Svenningsson, A.
    Olsson, T.
    Piehl, F.
    Blennow, K.
    Lycke, J.
    Neurofilament light in serum for monitoring multiple sclerosis: A new quantitative tool for measuring disease activity and therapeutic response2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, p. 577-577Article in journal (Other academic)
  • 38. Novakova, Lenka
    et al.
    Zetterberg, Henrik
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Axelsson, Markus
    Khademi, Mohsen
    Gunnarsson, Martin
    Malmestrom, Clas
    Svenningsson, Anders
    Olsson, Tomas
    Piehl, Fredrik
    Blennow, Kaj
    Lycke, Jan
    Monitoring disease activity in multiple sclerosis using serum neurofilament light protein2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, no 22, p. 2230-2237Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS). Methods: NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the Uman Diagnostics NF-light enzyme-linked immunosorbent assay. The serum NFL concentration was measured with an in-house ultrasensitive single-molecule array assay. Results: In MS, the correlation between serum and CSF NFL was r = 0.62 (p< 0.001). Serum concentrations were significantly higher in patients with relapsing-remitting MS (16.9 ng/L) and in patients with progressive MS (23 ng/L) than in HCs (10.5 ng/L, p< 0.001 and p< 0.001, respectively). Treatment with DMT reduced median serum NFL levels from 18.6 (interquartile range [IQR] 12.6-32.7) ng/L to 15.7 (IQR 9.6-22.7) ng/L (p< 0.001). Patients with relapse or with radiologic activity had significantly higher serum NFL levels than those in remission (p< 0.001) or those without new lesions on MRI (p< 0.001). Conclusions: Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.

  • 39. Petersson, Malin
    et al.
    Feresiadou, Amalia
    Jons, Daniel
    Ilinca, Andreea
    Lundin, Fredrik
    Johansson, Rune
    Budzianowska, Anna
    Roos, Anna-Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Kågström, Viktor
    Gunnarsson, Martin
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Piehl, Fredrik
    Brauner, Susanna
    Patient-reported symptom severity in a nationwide myasthenia gravis cohort: cross-sectional analysis of the Swedish GEMG study2021In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 97, no 14, p. e1382-e1391Article in journal (Refereed)
    Abstract [en]

    Background and Objectives: To describe myasthenia gravis activities of daily living (MG-ADL) in relation to clinical characteristics in a large Swedish nationwide cohort.

    Methods: In a cross-sectional prevalence cohort study, the Genes and Environment in Myasthenia Gravis study, performed from November 2018 through August 2019, patients with myasthenia gravis (MG) were invited to submit an extensive 106-item life environment questionnaire, including the MG-ADL score. Patients were classified into early-onset MG (EOMG, <50 years), late-onset MG (LOMG, >= 50 years), or thymoma-associated MG (TAMG). Comparisons of disease-specific characteristics were made between subgroups, sexes, and different MG-ADL scores.

    Results: A total of 1,077 patients were included, yielding a 74% response rate: 505 (47%) were classified as EOMG, 520 (48%) LOMG, and 45 (4%) TAMG. Mean age at inclusion was 64.3 years (SD 15.7) and mean disease duration was 14.6 years (SD 14.0). Complete MG-ADL scores (n = 1,035) ranged from 0p to 18p, where 26% reported a score of 0p. Higher MG-ADL scores were associated with female sex, obesity, and diagnostic delay (odds ratio [OR] 1.62, 1.72, and 1.69; p(adj) = 0.017, 0.013, and 0.008) and inversely correlated with high educational attainment (OR 0.59; p(adj) = 0.02), but not with age at inclusion, disease subtype, or disease duration. Almost half of the population (47%) reported MG-ADL >= 3p, corresponding to an unsatisfactory symptom state.

    Discussion: In this nationwide study, comprising more than 40% of the prevalent MG population in Sweden, almost half of the patients reported current disease symptoms associated with an unsatisfactory symptom state, indicating the need for improved treatment options.

    Download full text (pdf)
    fulltext
  • 40. Piehl, Fredrik
    et al.
    Eriksson-Dufva, Ann
    Budzianowska, Anna
    Feresiadou, Amalia
    Hansson, William
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hietala, Max Albert
    Håkansson, Irene
    Johansson, Rune
    Jons, Daniel
    Kmezic, Ivan
    Lindberg, Christopher
    Lindh, Jonas
    Lundin, Fredrik
    Nygren, Ingela
    Punga, Anna Rostedt
    Press, Rayomand
    Samuelsson, Kristin
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Wickberg, Oskar
    Brauner, Susanna
    Frisell, Thomas
    Efficacy and safety of rituximab for new-onset generalized myasthenia gravis: the RINOMAX randomized clinical trial2022In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 79, no 11, p. 1105-1112Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown.

    OBJECTIVE: To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG.

    DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids.

    INTERVENTIONS: Participants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo.

    MAIN OUTCOMES AND MEASURES: Minimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment.

    RESULTS: Of 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event.

    CONCLUSIONS AND RELEVANCE: A single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment.

    Download full text (pdf)
    fulltext
  • 41. Rosjo, E.
    et al.
    Lossius, A.
    Abdelmagid, N.
    Lindstrom, J. C.
    Kampman, M. T.
    Jorgensen, L.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olsson, T.
    Steffensen, L. H.
    Torkildsen, O.
    Holmoy, T.
    Selective and transient effect of vitamin D-3 supplementation on antibody responses against Epstein-Barr virus nuclear antigen 1 in relapsing-remitting multiple sclerosis2016In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 500-500Article in journal (Refereed)
  • 42. Rosjo, Egil
    et al.
    Lossius, Andreas
    Abdelmagid, Nada
    Lindstrom, Jonas C.
    Kampman, Margitta T.
    Jorgensen, Lone
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olsson, Tomas
    Steffensen, Linn H.
    Torkildsen, Oivind
    Holmoy, Trygve
    Effect of high-dose vitamin D-3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis2017In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 3, p. 395-402Article in journal (Refereed)
    Abstract [en]

    Background: Elevated antibody levels against Epstein–Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology.

    Objectives: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS.

    Methods: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385–420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473).

    Results: The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p < 0.001). Compared to the placebo group, both anti-EBNA1 protein and fragment antibody levels decreased in the vitamin D group from baseline to week 48 (p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV.

    Conclusion: The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

  • 43.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vitamin D and multiple sclerosis: where do we go from here?2014In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 14, no 1, p. 9-18Article, review/survey (Refereed)
    Abstract [en]

    This article briefly introduces the basics of multiple sclerosis' (MS) clinical hallmarks and pathophysiology. Vitamin D is presented, including its metabolism and effects on the immune system. The epidemiological observations linking vitamin D to MS range from a half century old findings of latitude gradients and migrational risk patterns to modern, nested, case-control biobank studies. These observations show an association without doubt although causation has yet to be proven. Vitamin D as a treatment for MS is an emerging concept and both current and anticipated data will be covered. Lastly, we discuss future challenges, ideas on how to move from association to causation, and the prospect of primary prevention of this disabling disease.

  • 44.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, A.
    Prevention of post-dural puncture headache: a randomized controlled trial2020In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 27, p. 14-15Article in journal (Other academic)
  • 45.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Department of Clinical Sciences, Danderyd Hospital AB, Karolinska Institutet Danderyd Hospital, Stockholm,Sweden.
    Prevention of post-dural puncture headache: a randomized controlled trial2020In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 27, no 5, p. 871-877Article in journal (Refereed)
    Abstract [en]

    Background and purpose: We investigated 952 subjects undergoing diagnostic lumbar puncture (LP) to study the effects of needle size, needle design and stylet reinsertion on the risk of post‐dural puncture headache (PDPH).

    Methods: This randomized double‐blind study was performed at Umeå University Hospital in Sweden during 2013–2018. Subjects were randomly assigned one of three needles [22 gauge (G) atraumatic, 25G atraumatic and 25G cutting] and stylet reinsertion before needle withdrawal or not. The main outcome measure was PDPH assessed by standardized telephone interview(s) 5 days after the LP, repeated until headache cessation. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PDPH.

    Results: The mean (SD) age was 51.1 (16.7) years and 53.6% were females. The smaller bore (25G) atraumatic needle incurred a lower risk of headache compared with the larger bore (22G) atraumatic needle [22.0% (69/314) vs. 30.2% (98/324); OR, 0.65; 95% CI, 0.45–0.93] and compared with the cutting needle [32.8% (103/314); OR, 0.58; 95% CI, 0.40–0.82]. Reinserting the stylet before needle withdrawal did not reduce the risk of headache.

    Conclusions: These data suggest that a 25G atraumatic needle is superior to a larger atraumatic needle, and to a same‐sized cutting needle, in preventing PDPH after diagnostic LP. In contrast to one earlier report, this study did not find that stylet reinsertion was effective in preventing PDPH. This study provides class I evidence that a small atraumatic needle decreases the risk of PDPH and that stylet reinsertion does not influence PDPH risk.

    Download full text (pdf)
    fulltext
  • 46.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Smoking as a risk factor for multiple sclerosis2013In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, p. 1022-1027Article in journal (Refereed)
    Abstract [en]

    Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure.

    Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples.

    Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression.

    Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8).

    Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

    Download full text (pdf)
    fulltext
  • 47.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vitamin A and systemic inflammation as protective factors in multiple sclerosis2013In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, p. 1046-1051Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin A is important for the immune system, and might suppress inflammatory activity in multiple sclerosis (MS).

    Objectives: We aimed to examine if vitamin A levels were associated with MS risk in samples collected prospectively and during gestation.

    Methods: We measured Retinol Binding Protein (RBP – a surrogate marker for vitamin A) and high-sensitivity C-reactive protein (hs-CRP) levels, in (1) prospectively collected biobank blood samples from MS cases and controls, and (2) gestational samples where the offspring had later developed MS, and gestational control samples. The risk of MS was calculated using matched multivariable logistic regression adjusted for confounders.

    Results: In prospective samples, RBP levels within the second quintile (vs. the first) were associated with a lower MS risk (OR = 0.38, 95% CI 0.19–0.74). No effect on MS risk in the offspring by gestational RBP levels was found. In young subjects hs-CRP levels ≥10 mg/l in prospective samples were associated with a lower MS risk (OR = 0.36, 95% CI 0.14–0.95).

    Conclusions: Our results suggest that sub-optimal vitamin A levels may be associated with MS risk. The association between hs-CRP levels and MS risk in young subjects may support the role of the hygiene hypothesis in MS aetiology. 

    Download full text (pdf)
    fulltext
  • 48.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vitamin D as a protective factor in multiple sclerosis2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, no 21, p. 2140-2145Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the association between 25-hydroxyvitamin D (25[OH]D) levels and the risk of multiple sclerosis (MS) in blood samples collected prospectively and during gestation.

    Methods: In this nested case-control study, 2 population-based biobanks with 291,500 samples from164,000 persons collected since 1975 in the northern half of Sweden were used. We identified prospectively collected blood samples from MS cases (n = 192, controls matched 2:1) and gestational samples from pregnant mothers where the offspring had later developed MS (n = 37, control mothers matched 5:1). 25(OH)D levels were measured using an ELISA, and the risk of MS was analyzed using matched logistic regression.

    Results: Levels of 25(OH)D ≥75 (vs <75) nmol/L in prospectively collected blood samples were associated with a decreased risk of MS (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.16- 0.98). No decrease in MS risk was found in the offspring exposed to gestational 25(OH)D levels ≥75 (vs <75) nmol/L (OR 1.8, 95%CI 0.53-5.8). The prevalence of 25(OH)D levels ≥75 nmol/L in female controls decreased gradually during 1976-2005 (p trend = 0.005).

    Conclusion: This study supports the presence of an association between high 25(OH)D levels during the years preceding disease onset and a decreased risk of MS. In the very limited material with samples drawn in early pregnancy, where month-of-birth effects were controlled for, we found no association between gestational 25(OH)D levels and MS risk in the offspring. Decreasing 25(OH) D levels in the population may contribute to explain the increasing MS incidence that is suggested from epidemiologic studies.

  • 49.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels2013In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 12, p. 1587-1591Article in journal (Refereed)
    Abstract [en]

    Background: Increased antibody reactivity against Epstein-Barr Nuclear Antigen-1 (EBNA-1) has been associated with an increased risk for MS, and high levels of 25-Hydroxyvitamin D (25[OH]D) have been associated with a lower risk for MS. Interaction between these two factors has been proposed.

    Objectives: To examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk for multiple sclerosis (MS), and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.

    Methods: Antibody reactivity (as specified above) and 25(OH)D levels were measured using ELISAs in n=192 MS cases and n=384 matched controls. The risk for MS was analysed using matched logistic regression.

    Results: The risk for MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trend <0.001. The risk increase was most pronounced for EBNA-1385–420. In young individuals (below median age at sampling, <26.4 years) these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains.

    Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor for MS. Our findings in young individuals suggest that 25(OH)D status might influence the immune response towards Epstein-Barr virus, and thereby modulate MS risk.

    Download full text (pdf)
    fulltext
  • 50.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rajda, C.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vecsei, L.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Are we minimizing the patients' risk for headache?: a lumbar puncture practice questionnaire study among European neurologists2015In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, p. 733-734Article in journal (Other academic)
12 1 - 50 of 83
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf