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  • 1. Askling, Johan
    et al.
    Holmqvist, Marie
    Ljung, Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Is Rheumatoid Arthritis a Mortal Disease?2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no 8, p. 1509-1511Article in journal (Other academic)
  • 2. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Lie, Elisabeth
    Klingberg, Eva
    Dehlin, Mats
    Exarchou, Sofia
    Lindstrom, Ulf
    Askling, Johan
    Jacobsson, Lennart T. H.
    Are Ankylosing Spondylitis, Psoriatic Arthritis and Undifferentiated Spondylarthritis Associated with an Increased Risk of Cardiovascular Disease?2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, article id 1057Article in journal (Other academic)
  • 3. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Lie, Elisabeth
    Klingberg, Eva
    Dehlin, Mats
    Exarchou, Sofia
    Lindstrom, Ulf
    Askling, Johan
    Jacobsson, Lennart T. H.
    Increased Risk of Atrioventricular Block, Atrial Fibrillation and Pacemaker Implantation in Ankylosing Spondylitis, Undifferentiated Spondylarthritis and Psoriatic Arthritis Compared to the General Population2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no 10, article id 1059Article in journal (Other academic)
  • 4.
    Boman, Antonia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Kokkonen, Heidi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Berglin, Ewa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Ärlestig, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Sclerostin Are Related to Joint Destruction in Early Rheumatoid Arthritis Unrelated to Polymorphisms of the Genes2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no 10, article id 3101Article in journal (Other academic)
  • 5. Di Giuseppe, Daniela
    et al.
    Ljung, Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Sundström, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Meat Consumption and Risk of Rheumatoid Arthritis in Women: A Population-Based Cohort Study2018In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, no S9, article id 203Article in journal (Other academic)
    Abstract [en]

    Background/Purpose: Mixed results have been reported for the association between meat consumption and the risk of developing rheumatoid arthritis (RA). The aim of this study was to evaluate the association between red meat, particularly processed meat, and the risk of RA using data from a population-based cohort of women.

    Methods: We prospectively followed 35,600 women aged 48-83 years from the Swedish Mammography Cohort (SMC), between 2003 and 2014. Meat consumption was assessed with a 96-item self-administered questionnaire in 1997. A corresponding questionnaire data from 1987 was available, enabling identification of long-term meat consumption. The relative risk (RR) of RA associated with meat consumption and its 95% confidence interval (CI) were estimated using Cox proportional hazard regression models. Multivariable models were adjusted for age, body mass index, educational level, physical activity, use of dietary supplements, energy intake, and smoking.

    Results: During the 12 years of follow-up (381 456 person years), 368 new cases of rheumatoid arthritis were identified. Meat consumption was not associated with the development of RA in age-adjusted (RR=0.96 (95% CI: 0.69-1.32)) or multivariable adjusted (RR=1.08 (95%CI: 0.77-1.53)) models (Table 1). No association was observed either for consumption of type-specific meat, such as red meat (RR=1.08 (95% CI: 0.77-1.50)), processed meat (RR=0.84 (95% CI: 0.59-1.22)), or poultry (RR=0.88 (95% CI: 0.60-1.31)). , Women with a consistent long-term consumption of meat of >7 servings/week over a period of 10 years had no increased risk of RA, HR 1.19 (95% CI: 0.78-1.80), compared to women with a consistent consumption of <=4 servings/week.

    Conclusion: In this large population-based cohort study, meat consumption, in total, by sub-types, or over time, was not associated with the risk of RA development in women.

  • 6. Jiang, Xia
    et al.
    Sundström, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Alfredsson, Lars
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Bengtsson, Camilla
    Sodium Chloride Consumption, Together with Smoking, Is Associated with ACPA Positivity2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, article id 2018Article in journal (Other academic)
  • 7.
    Johansson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Sherina, Natalia
    Kharlamova, Nastya
    Larsson, Barbro
    Israelsson, Lena
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Lundberg, Karin
    Plasma Concentrations of Antibodies to Porphyromonas Gingivalis Are Increased before Onset of Symptom of Rheumatoid Arthritis2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, article id 524Article in journal (Other academic)
  • 8.
    Kindstedt, Elin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Linda
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Palmqvist, Py
    Umeå University, Faculty of Medicine, Department of Odontology.
    Koskinen Holm, Cecilia
    Umeå University, Faculty of Medicine, Department of Odontology.
    Kokkonen, Heidi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Marginal Jawbone Loss Predates the Onset of Rheumatoid Arthritis2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69Article in journal (Other academic)
    Abstract [en]

    Background/Purpose: Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid arthritis (RA) and that patients with periodontitis are at a greater risk for developing RA. Periodontitis, displayed as marginal jawbone loss was analysed in individuals prior to symptom onset of RA and related to plasma levels of receptor activator of nuclear factor kappa-B (RANKL), a cytokine crucial for bone resorption. Methods: A case-control study performed within the Medical Biobank of Northern Sweden included 232 pre-symptomatic individuals with blood samples donated before symptom onset and 194 controls. A questionnaire on self-assed dental status and smoking status was retrieved. Dental radiographs to evaluate marginal jawbone levels were available from 93 pre-symptomatic individuals (mean age; 56.8 95%CI55.9, 57.7 years and pre-dating time; -5.3 95%CI -12.2, -0.2, 74.2% females) and 83 controls (mean age; 55.5 95%CI54.6, 56.5, 73.5% females) . Of these individuals 45 had radiograph documentations prior to development of RA symptoms and to whom sex, age and smoking status could be matched among the controls. Plasma were analysed for RANKL (BioVendor, Karasek, Czech Republic), and anti-citrullinated peptide antibodies (ACPA) (anti-CCP2 test, Eurodiagnostics, Sweden) from similar time points. Results: Compared to matched controls, total bone loss was significantly higher in never-smokers who developed RA but not in smokers and increasing levels on total jawbone loss was associated with a significantly higher odds to be diagnosed with RA later (OR=1.06, 95%CI 1.01, 1.11). Regardless of smoking status, the number of unaffected teeth did not differ significantly between those who were subsequently diagnosed with RA and their matched controls. In the pre-symptomatic individuals RANKL positive individuals had significantly higher extent of marginal jawbone loss, which was further increased in ACPA positive individuals. Previously documented association between smoking and ageing and marginal jawbone loss was verified. Conclusion: Marginal jawbone loss preceded onset of symptoms of RA but the difference was only manifested in non-smokers. Moreover, marginal jawbone loss and plasma RANKL levels were related in the pre-symptomatic individuals particularly in ACPA positive individuals.

  • 9.
    Kindstedt, Elin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Linda
    Palmqvist, Py
    Umeå University, Faculty of Medicine, Department of Odontology.
    Koskinen Holm, Cecilia
    Umeå University, Faculty of Medicine, Department of Odontology.
    Kokkonen, Heidi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL2018In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, no 4, p. 508-515Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.

    Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme‐linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.

    Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL‐positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.

    Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL‐positive presymptomatic subjects compared with RANKL‐negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.

  • 10.
    Kokkonen, Heidi
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Johansson, Linda
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Inflammatory Markers in Relation to Risk Factors for Cardiovascular Disease in the Pre-Symptomatic Phase of Rheumatoid Arthritis2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69Article in journal (Other academic)
    Abstract [en]

    Background/Purpose: Individuals who later developed rheumatoid arthritis (RA) have increased levels and frequencies of risk factors for cardiovascular disease (CVD), years before onset of RA. The relationships between CVD risk factors and inflammatory markers, i.e., cytokines and chemokines, were analysed in individuals prior to onset of symptoms and compared with controls. Methods: A case-control study was based on population surveys from The Västerbotten Intervention Programme (VIP) and the WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) with data collected on socioeconomic and lifestyle factors, BMI, waist, blood pressure, and blood samples by a nurse. The register of patients with RA (ARA criteria) was co-analysed with the registers from the Medical Biobank and 469 pre-symptomatic individuals (median age 50.2 years; 67.8% women, median predating time 5.0 (IQR; 2.0-8.0) years), and 234 controls (median age 50.3 years; 67.1% women) were identified. CVD risk factors were defined as: hypertension (treatment or systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg), elevated ApoB/ApoA1 ratio (women ≥0.7, men ≥0.8, including lipid lowering treatment), BMI ≥25kg/m2, diabetes, and ever being smoker. Concentrations of eotaxin, interferon gamma-induced protein (IP-10), monocyt-chemoattractant protein 1 (MCP1), macrophage derived chemokine (MDC), interleukin (IL) 2, IL-4, IL-6, IL-8, and IL-10, were analysed in plasma using R&D systems' assays (Minneapolis, MN) according to the manufacturer's instructions. Results: Pre-symptomatic individuals had significantly higher levels of IL-6 compared with controls, both in women and men. IL-10 was significantly higher in pre-symptomatic men compared with controls. Cytokines/chemokines were significantly associated with the CVD risk factors in the cases e.g. IL-6 with each of the risk factors, eotaxin with smoking, IP-10 with increased BMI, being diabetes or having hypertension, whilst MDC was associated significantly with smoking and BMI≥25 kg/m2. After adjustments for sex and age only eotaxin concentrations were significantly associated with being ever smoker. In women, MDC was significantly associated with smoking, BMI≥25 kg/m2 and diabetes. Having the combination of several CVD risk factors was associated with significantly higher concentrations of MCP-1, MDC, and IL-6 in pre-symptomatic women. IL-6 increased further the relative risk in combinations with all CVD risk factors for the pre-symptomatic cases compared with controls. Conclusion: Increased concentrations of cytokines/chemokines were associated with CVD risk factors to a higher extent among the pre-symptomatic RA cases compared with controls. The pattern of association varied between the risk factors and the sex of the cases.

  • 11. Lie, Elisabeth
    et al.
    Lindstrom, Ulf
    Zverkova-Sandstrom, Tatiana
    Olsen, Inge C.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Askling, Johan
    Kristensen, Lars Erik
    Jacobsson, Lennart T. H.
    The Effect of TNF Inhibitor Treatment on Occurrence of Anterior Uveitis in Ankylosing Spondylitis: Results from the Swedish Biologics Register2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, article id 973Article in journal (Other academic)
  • 12.
    Ljung, Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Department of Medicine, Solna, Clinical epidemiology unit, Karolinska Institutet, Stockholm, Sweden.
    Frisell, Thomas
    Askling, Johan
    The Link Between DAS28 and the Short-Term Risk of Acute Coronary Syndrome in RA, and Its Driving Factors2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, article id 3257Article in journal (Other academic)
  • 13.
    Ljung, Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Department of Medicine, Solna, Clinical epidemiology unit, Karolinska Institutet, Stockholm, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Obesity and the Risk for Development of Rheumatoid Arthritis - Results from a Population-Based Nested Case-Control Study2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, article id 1598Article in journal (Other academic)
  • 14. Mantel, Angla
    et al.
    Holmqvist, Marie
    Jernberg, Tomas
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Askling, Johan
    Secondary Preventive Pharmacotherapy and Longterm Outcomes Following Acute Coronary Events in Patients with Prevalent Rheumatoid Arthritis2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, article id 912Article in journal (Other academic)
  • 15. Ramirez, Jorge
    et al.
    Kvarnstrom, Marika
    Brauner, Susanna
    Baldini, Chiara
    Eriksson, Per
    Mandl, Thomas
    Norheim, Katrine Brække
    Johnsen, Svein Joar
    Hammenfors, Daniel S.
    Jonsson, Malin V.
    Skarstein, Kathrine
    Brun, Johan G.
    Rönnblom, Lars
    Forsblad D'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Bucher, Sara Magnusson
    Theander, Elke
    Omdal, Roald
    Jonsson, Roland
    Nordmark, Gunnel
    Wahren-Herlenius, Marie
    Difference in Clinical Presentation between Female and Male Patients with Primary Sjogren's Syndrome at Diagnosis and in Long-Term Follow-up2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69Article in journal (Other academic)
    Abstract [en]

    Background/Purpose: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to identify differences in clinical presentation between the sexes at the time of diagnosis and during long-term follow-up of primary Sjögren's syndrome (pSS), and to establish whether male sex is associated with a more severe form of pSS. Methods: Incident, treatment naïve patients (n=199, 186 females and 13 males) from Stockholm, Sweden were prospectively included during a 5-year period and examined for items of classification criteria for pSS as well as extraglandular manifestations (EGM). Serum was sampled at the time of diagnosis and anti-Ro52/SSA levels measured by ELISA. Replication of significant findings was confirmed in an independent cohort of incident pSS patients from Pisa, Italy (n=377, 368 females and 9 males), and meta-analysis performed. We further studied a cohort of 967 patients with prevalent pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 ± 7.6 for women and 8.5 ± 6.2 for men (ns). Clinical data including serological and hematological parameters, glandular, EGM and comorbidities were compared between men and women. Results: An increased frequency of EGM in men at diagnosis was observed and replicated (p=0.05, p=0.0003, and pmeta=0.002, respectively). This related to pulmonary involvement, vasculitis and lymphadenopathy being more common in men, for whom a lower age at diagnosis was observed in the exploratory cohort. Additionally, SSA positive male patients had significantly higher levels of anti-Ro52 levels than their female counterparts (p=0.02). After long-term follow-up, male patient serology was characterized by more frequent positivity for anti-SSA and anti-SSB (p=0.02), and ANA (p=0.02). Also, men with pSS were more frequently diagnosed with interstitial lung disease (p=0.008), lymphadenopathy (p=0.04) and lymphoma (p=0.007). Conversely, concomitant hypothyroidism was more common among female patients (p=0.009). Conclusion: Our analysis of two independent cohorts of incident pSS and a large cohort of prevalent pSS demonstrates significant differences between women and men with pSS. Notably, men present with more EGM, enhanced serological profile and a higher frequency of lymphoma development.

  • 16. Reid, Sarah
    et al.
    Alexsson, Andrei
    Frodlund, Martina
    Sandling, Johanna K.
    Svenungsson, Elisabet
    Jönsen, Andreas
    Bengtsson, Christine
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Gunnarsson, Iva
    Bengtsson, Anders A.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Eloranta, Maija-Leena
    Syvänen, Ann-Christine
    Sjöwall, Christopher
    Rönnblom, Lars
    Leonard, Dag
    High Genetic Risk Score Is Associated with Increased Organ Damage in SLE2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69Article in journal (Other academic)
    Abstract [en]

    Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease with a complex genetic etiology. Over 80 risk genes for SLE have been identified and some genetic variants have demonstrated association with specific disease manifestations, such as STAT4 and nephritis. The overall effect of a patient’s hereditary risk factors on disease severity has so far not been studied. We therefore assessed the relationship between high genetic risk and development of organ damage in SLE. Methods: Patients with SLE, who met at least 4 ACR criteria (n = 1012), were genotyped using a 200K Immunochip SNP Array (Illumina). A genetic risk score (GRS) was assigned to each patient based on the single nucleotide polymorphisms (SNPs) which in previous studies have shown association (p<5×10-8) with SLE according to Morris, et al (Nat Genet, 2016. 48(8): p. 940-6). For 32 loci the SLE GWAS SNP was available on the ImmunoChip. For each SNP, the natural logarithm of the odds ratio (OR) for SLE susceptibility was multiplied by the number of risk alleles in each individual. The sum of all products for each patient was defined as the GRS. Information regarding organ damage according to Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SLICC-DI), disease manifestations, antibody profile, medication, current disease activity, age at diagnosis and sex was retrieved from medical records. Statistical analyzes were performed using Statistica 13.2 (Statsoft). Results: In an ordinal regression model, with SLICC-DI (0, 1, 2, 3, 4 and >4 points) as outcome and age and GRS as independent variables, an association was found between GRS and SLICC-DI (OR1.16 (1.03-1.31), p=0.015). The relationship was more pronounced for patients under 60 years of age (OR1.30 (1.11-1.52) p=7.1×10-4). Using a linear regression model, a negative relationship was observed between GRS and age at diagnosis (β = -0.13, p=1.5×10-5).When analyzing the 11 SLE criteria (ACR-82) using a logistic regression model associations were observed between GRS and nephritis (OR 1.26 (1.09-1.45), p=0.0015), the immunological criteria (OR 1.31 (1.13-1.51), p = 3.2×10-4) and arthritis (OR 0.84 (0.71-1.00), p=0.044). A high GRS was also associated with presence of anti-dsDNA (OR 1.37 (1.15-1.62), p=9.4×10-7) and low complement levels (OR 1.32 (1.03-1.68), p=0.044). No association was observed between GRS and disease activity at the time of follow-up and there was no difference in GRS between men and women with SLE. Conclusion: In patients with SLE, there is an association between a high genetic risk score and early disease onset. In addition, patients with high genetic risk scores have a higher risk of developing permanent organ damage compared to individuals with fewer risk genes. Our findings indicate that genetic profiling of patients with SLE may provide a tool for predicting severity of the disease.

  • 17. van Steenbergen, H. W.
    et al.
    Raychaudhuri, S.
    Rodríguez-Rodríguez, L.
    Rantapää-Dahlqvist, Solbritt
    Berglin, Ewa
    Toes, R. E. M.
    Huizinga, T. W. J.
    Fernández-Gutiérrez, B.
    Gregersen, P. K.
    van der Helm-van Mil, A. H. M.
    Association of valine and leucine at HLA-DRB1 position 11 with radiographic progression in rheumatoid arthritis, independent of the shared epitope alleles but not independent of anti-citrullinated protein antibodies2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no 4, p. 877-886Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status.

    METHODS: A total of 4,911 radiograph sets from 1,878 RA patients included in the Leiden Early Arthritis Clinic (The Netherlands), Umeå (Sweden), Hospital Clinico San Carlos-Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US) cohorts were studied. HLA was imputed using single-nucleotide polymorphism data from an Immunochip, and the amino acids listed above were tested in relation to radiographic progression per cohort using an additive model. Results from the 4 cohorts were combined in inverse-variance weighted meta-analyses using a fixed-effects model. Analyses were conditioned on SE and ACPA status.

    RESULTS: Val and Leu at HLA-DRB1 position 11 were associated with more radiographic progression (meta-analysis P = 5.11 × 10(-7)); this effect was independent of SE status (meta-analysis P = 0.022) but not independent of ACPA status. Phe at HLA-DPB1 position 9 was associated with more severe radiographic progression (meta-analysis P = 0.024), though not independent of SE status. Asp at HLA-B position 9 was not associated with radiographic progression.

    CONCLUSION: Val and Leu at HLA-DRB1 position 11 conferred a risk of a higher rate of radiographic progression independent of SE status but not independent of ACPA status. These findings support the relevance of these amino acids at position 11.

  • 18. Verheul, Marije K.
    et al.
    Böhringer, Stefan
    van Delft, Myrthe A. M.
    Jones, Jonathan D.
    Rigby, William F. C.
    Gan, Ryan W.
    Holers, V. Michael
    Edison, Jess D.
    Deane, Kevin D.
    Janssen, Koen M. J.
    Westra, Johanna
    Brink, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Huizinga, Tom W. J.
    van der Helm-van Mil, Annette H. M.
    van der Woude, Diane
    Toes, Rene E. M.
    Trouw, Leendert A.
    Triple positivity for anti–citrullinated protein autoantibodies, rheumatoid factor, and anti–carbamylated protein antibodies conferring high specificity for rheumatoid arthritis: implications for very early identification of at‐risk individuals2018In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, no 11, p. 1721-1731Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In rheumatoid arthritis(RA), the autoantibodies anti-citrullinated protein antibodies(ACPA) and rheumatoid factor(RF) are commonly used to aid RA diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPA and RF alone. Also, anti-carbamylated protein(anti-CarP) antibodies have diagnostic and prognostic value as the presence of anti-CarP antibodies associates with joint damage in RA patients and with future RA development in arthralgia patients. Therefore, we aimed to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA.

    METHODS: A literature search resulted in twelve studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients or healthy controls, in which data on RF, ACPA and anti-CarP antibody-status was available. Random effects meta-analyses were carried out for several antibody combinations.

    RESULTS: The individual antibodies are highly prevalent in RA(34%-80%) compared to the control groups, but are also present in non-RA controls(0%-23%). To classify most people correctly as RA or non-RA, the combination of ACPA and/or RF often performs well(specificity:65-100, sensitivity:59-88). However, triple positivity for ACPA, RF and anti-CarP antibodies results in a higher specificity(98-100) (accompanied by a lower sensitivity(11-39)).

    CONCLUSIONS: As the rheumatology field is moving towards very early identification of RA and possible screening for individuals at maximum risk in populations with a low pre-test probability, triple positivity provides interesting information on individuals at risk to develop RA.

  • 19. Westra, Harm-Jan
    et al.
    Martinez-Bonet, Marta
    Onengut, Suna
    Lee, Annette
    Luo, Yang
    Teslovich, Nikola
    Worthington, Jane
    Martin, Javier
    Huizinga, T. W. J.
    Klareskog, Lars
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Chen, Wei-Min
    Quinlan, Aaron
    Todd, John
    Eyre, Stephen
    Nigrovic, Peter
    Gregersen, Peter
    Rich, Stephen
    Raychaudhuri, Soumya
    Fine-Mapping Identifies Causal Variants for RA and T1D in DNASE1L3, Sirpg, MEG3, TNFAIP3 and CD28/CTLA4 Loc2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69Article in journal (Other academic)
  • 20. Wibetoe, Grunde
    et al.
    Crowson, Cynthia S.
    Sexton, Joseph
    Rollefstad, Silvia
    Ikdahl, Eirik
    Kitas, George D.
    van Riel, Piet
    Gabriel, Sherine E.
    Kvien, Tore K.
    Douglas, Karen
    Sandoo, Aamer
    Arts, Elke
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Karpouzas, George
    Dessein, Patrick H.
    Tsang, Linda
    El-Gabalawy, Hani
    Hitchon, Carol A.
    Pascual-Ramos, Virginia
    Contreras-Yanez, Irazu
    Sfikakis, Petros P.
    Zampeli, Evangelia
    Angel Gonzalez-Gay, Miguel
    Corrales, Alfonso
    Colunga-Pedraza, Iris J.
    Galarza-Delgado, Dionicio A.
    Ramon Azpiri-Lopez, Jose
    Semb, Anne Grete
    Performance of Cardiovascular Risk Age and Vascular Age Estimations in Predicting Cardiovascular Events in Rheumatoid Arthritis2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69Article in journal (Other academic)
    Abstract [en]

    Background/Purpose: Rheumatoid arthritis (RA) patients are at high risk of cardiovascular disease (CVD). Risk algorithms for the general population lack precision when applied to RA patients and validated RA-specific CVD prediction models are missing. Risk age estimations are recommended as adjuncts to assessment of absolute 10-year risk of fatal CVD events. Two risk age models based on the Systematic Coronary Risk Evaluation (SCORE) algorithm have been developed; the cardiovascular risk age and the vascular age. However, the performance of these models has not been compared. Using longitudinal data on CVD events in RA patients, we aimed to compare the discriminative ability of cardiovascular risk age and vascular age among RA patients and in subgroups of RA patients based on disease characteristics. Methods: Patients with RA were included from an international consortium, aged 30-70 years at baseline. Those with prior CVD, diabetes and/or users of lipid-lowering and/or antihypertensive therapy at baseline were excluded. Cardiovascular risk age was estimated based on chronologic age, smoking status, total cholesterol and systolic blood pressure at baseline. Vascular age was derived from the 10-year risk of CVD according to the SCORE algorithm, with or without high density lipoprotein cholesterol, using the equations for low and high risk countries. Performance of each risk age model in predicting CVD events was assessed using the concordance index. Results: Among the1867 RA patients included, 74% were female, median (inter-quartile range) age and disease duration were 52.0 (44.0, 59.9) and 0.6 (0.1, 6.4) years, 72.5% were rheumatoid factor positive, 24.7% were using glucocorticoids and 10.3% were using biologics at baseline. Overall, 144 CVD events occurred and median follow-up time was 5.0 (2.6, 9.3) years. Median difference between estimated risk age and chronologic age was 4.0 to 6.7 years, depending on the specific risk age model applied. Overall, the C-index across risk models ranged from 0.71 to 0.73 with standard errors of 0.03. Across prediction models, the lowest observed concordance was found among women and in glucocorticoid users and in those with new-onset disease (≤1 year). Additional analyses including RA patients on cardio preventive therapy yielded slightly lower c-indexes. Since SCORE was developed for use in Europe, we performed analyses on European RA patients, which yielded similar results. The trend of reduced concordance among women, glucocorticoid users and RA patients with short disease duration was preserved in these additional analyses. Conclusion: The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. Sex, disease duration and/or glucocorticoid treatment may influence the performance of risk age estimations.

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