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Law, L., Lindqvist, P., Liv, P., Hellman, U., Lejon, K., Geijer, M., . . . Forsblad-d'Elia, H. (2024). Increased carotid intima-media thickness in patients with radiographic axial spondyloarthritis compared to controls and associations with markers of inflammation. Clinical Rheumatology, 43(5), 1559-1570
Öppna denna publikation i ny flik eller fönster >>Increased carotid intima-media thickness in patients with radiographic axial spondyloarthritis compared to controls and associations with markers of inflammation
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2024 (Engelska)Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 43, nr 5, s. 1559-1570Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: There is an increased risk for cardiovascular disease (CVD) in patients with radiographic axial spondyloarthritis (r-axSpA). In this cross-sectional study, we aimed to, overall and stratified by sex, (i) compare ultrasound derived carotid intima media thickness (cIMT), between patients and controls, and (ii) investigate associations between cIMT, clinical disease activity and inflammation-related laboratory markers in patients with r-axSpA.

Method: In total, 155 patients diagnosed with r-axSpA using the modified New York criteria and 400 controls were included. Bilateral carotid ultrasound, laboratory testing, and questionaries were acquired. Disease-specific assessments were carried out for patients. Linear regression analysis was used to assess associations.

Results: Linear regression analyses showed that patients with r-axSpA had increased mean cIMT compared to controls (mean ± SD, 0.8 ± 0.1 mm vs 0.7± 0.1 mm, respectively, unstandardized β (95% CI) -0.076 (-0.10, -0.052), P < 0.001) adjusted for smoking status and age. Linear regression analyses for patients with r-axSpA showed that only males presented significant associations between cIMT and inflammation-related laboratory markers, white blood cell (WBC) count (mean ± SD, 6.8 ± 1.6 109/L) and monocytes (0.6 ± 0.2 109/L); WBC count (unstandardized β (95% CI) 0.019 (0.0065, 0.031), P = 0.003, R2 = 0.57) and monocytes (0.13 (0.0047, 0.26), P = 0.041, R2 = 0.55), adjusted for age, smoking status, body mass index, hypertension, dyslipidemia, diabetes mellitus, ASDAS-CRP, and treatment with DMARDs and glucocorticoids. No significant association was found between cIMT and clinical disease activity assessed by ASDAS-CRP.

Conclusion: Patients with r-axSpA had significantly increased cIMT compared to controls. In male patients, higher WBC and monocyte count were associated with an increase in cIMT suggesting the role of inflammation in the development of atherosclerosis. 

Ort, förlag, år, upplaga, sidor
Springer Nature, 2024
Nyckelord
Cardiovascular disease (CVD), Carotid intima-media thickness (cIMT), Radiographic axial spondyloarthritis (r-axSpA), Ultrasound
Nationell ämneskategori
Kardiologi
Identifikatorer
urn:nbn:se:umu:diva-221778 (URN)10.1007/s10067-024-06913-8 (DOI)001176391500001 ()38443604 (PubMedID)2-s2.0-85186622797 (Scopus ID)
Forskningsfinansiär
VetenskapsrådetRegion VästerbottenStiftelsen Konung Gustaf V:s 80-årsfond
Tillgänglig från: 2024-03-06 Skapad: 2024-03-06 Senast uppdaterad: 2024-04-18Bibliografiskt granskad
Lejon, K., Hellman, U., Kumar, A. & Forsblad-d'Elia, H. (2023). Decreased levels of T follicular helper (CD4+CXCR5+) cells and CD27+CD38+ and CD27+CD38− B cells in ankylosing spondylitis patients correlate with markers of inflammation. Scandinavian Journal of Immunology, 97(1), Article ID e13235.
Öppna denna publikation i ny flik eller fönster >>Decreased levels of T follicular helper (CD4+CXCR5+) cells and CD27+CD38+ and CD27+CD38− B cells in ankylosing spondylitis patients correlate with markers of inflammation
2023 (Engelska)Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 97, nr 1, artikel-id e13235Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The purpose of this study was to study CD4+CXCR5+ T follicular helper (TFH) cells, CD27+CD38+ plasmablasts and CD27+CD38− memory B cells, as well as disease-related factors in patients with ankylosing spondylitis (AS) from northern Sweden. Peripheral blood mononuclear cells (PBMC) from 50 patients with AS (mean age 52 ± 9 years, 66% men, 100% HLA-B27 positive) and 50 pairwise matched blood donor controls (mean age 54 ± 9 years, 66% men) were stained with antibodies for CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analysed by flow cytometry. Patients with AS were examined with spinal x-ray for radiographic alterations (mSASSS), and plasma levels of C-reactive protein, erythrocyte sedimentation rate, as well as selected proinflammatory and regulatory cytokines were determined. Physical mobility, function and disease activity were registered by BASMI, BASFI and ASDAS-CRP, BASDAI, respectively. Comparing AS patients and controls pairwise, we observed a 56% reduction of TFH cells in PBMCs from AS patients (P =.000008). Furthermore, a 20%-30% reduction in plasmablasts and B memory cells (P ≤.002 and P ≤.007, respectively) was observed. In female patients, negative correlations between ESR and TFH, plasmablasts and B memory cells were observed; Rs = −0.551, P ≤.02; Rs = −0.476, P ≤.05 and Rs = −0.522, P ≤.03, respectively. In addition, positive correlations between the regulatory cytokine IL-10 and the proportion of B cells, IL-22, and the proportion of plasmablasts as well as a negative correlation between levels of the proinflammatory cytokine IL-6 and TFH were detected. Our observations indicate a role of an aberrant humoral immune response related to inflammation in AS.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2023
Nyckelord
ankylosing spondylitis, memory B cells, plasmablasts, radiographic axial spondyloarthritis, TFH
Nationell ämneskategori
Immunologi inom det medicinska området Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-201478 (URN)10.1111/sji.13235 (DOI)000889655600001 ()2-s2.0-85142643347 (Scopus ID)
Forskningsfinansiär
Stiftelsen Konung Gustaf V:s 80-årsfond, FAI2017-0454Region Västerbotten, ALFVLL-640251Vetenskapsrådet, 2016-02035
Tillgänglig från: 2022-12-06 Skapad: 2022-12-06 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Brink, M., Berglin, E., Mohammad, A. J., Lundquist, A., Gjertsson, I., Alexeyenko, A., . . . Rantapää-Dahlqvist, S. (2023). Protein profiling in presymptomatic individuals separates myeloperoxidase-antineutrophil cytoplasmic antibody and proteinase 3-antineutrophil cytoplasmic antibody vasculitides. Arthritis & Rheumatology, 75(6), 996-1006
Öppna denna publikation i ny flik eller fönster >>Protein profiling in presymptomatic individuals separates myeloperoxidase-antineutrophil cytoplasmic antibody and proteinase 3-antineutrophil cytoplasmic antibody vasculitides
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2023 (Engelska)Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 75, nr 6, s. 996-1006Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a chronic relapsing condition with unknown etiology. To gain insight into the molecular processes underlying the disease, we examined biomarkers in blood samples collected prior to symptom onset.

Methods: The National Patient Register and Cause of Death register were searched for AAV-related International Classification of Diseases, Ninth Revision and Tenth Revision codes and linked to the registers from 5 biobanks. Eighty-five AAV patients with samples predating symptom onset of AAV were identified. For each case of AAV, 2 matched controls were included. Proteinase 3 (PR3)–ANCA and myeloperoxidase (MPO)–ANCA expression levels were analyzed using enzyme-linked immunosorbent assays. Using an Olink Inflammation panel, 73 of 92 proteins were included after quality control. Data were replicated in a second cohort of 48 presymptomatic individuals and 96 controls.

Results: Of the 20 proteins with the lowest P values in the original cohort, 7 were replicated in the second cohort and 5 proteins were found to be significant between the groups in a meta-analysis. Eleven different pathways were identified in network enrichment analyses and were found to be significant in both cohorts. Stratification of samples obtained ≤5 years before symptom onset showed significant levels of CCL23, vascular endothelial growth factor A, and hepatocyte growth factor, which were also increased at borderline significant levels in the replication cohort (interleukin-6 was found to be significantly increased in the replication cohort). In presymptomatic AAV patients, 6 proteins were associated with MPO-ANCA positivity, and 7 proteins were associated with PR3-ANCA positivity.

Conclusion: To our knowledge, this is the first study to identify protein markers preceding symptom onset in AAV patients. These findings set the stage for further research into the underlying cellular and molecular mechanisms in the pathogenesis of AAV and the diversification of patients into PR3-ANCA+ and MPO-ANCA+ subphenotypes. (Figure presented.).

Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-211991 (URN)10.1002/art.42425 (DOI)000967341700001 ()36533851 (PubMedID)2-s2.0-85147033853 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2018-02551Stiftelsen Konung Gustaf V:s 80-årsfondUmeå universitetRegion Västerbotten
Tillgänglig från: 2023-07-12 Skapad: 2023-07-12 Senast uppdaterad: 2023-07-12Bibliografiskt granskad
Renman, E., Ekici, R., Sundström, M. & Lejon, K. (2022). HSC70 is a novel binding partner involved in the capture of immunoglobulins on B cells in the NOD mouse. Autoimmunity, 55(8), 520-528
Öppna denna publikation i ny flik eller fönster >>HSC70 is a novel binding partner involved in the capture of immunoglobulins on B cells in the NOD mouse
2022 (Engelska)Ingår i: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 55, nr 8, s. 520-528Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

B cells have been shown to be essential for Type 1 diabetes development in the non-obese diabetic mouse, where their contribution as antigen presenting cells has been emphasised. Other important functions for B cells include surface capture of immunoglobulins and transportation of immune complexes, with subsequent endocytosis, antigen processing and antigen presentation. We have previously demonstrated that NOD B cells capture IgM and IgG immune complexes through an unknown surface molecule. In this study, we revealed the presumptive immunoglobulin-binding molecule to be HSC70. Moreover, we detected increased levels of HSC70 on NOD B cells. HSC70 has been shown to play a role in antigen processing and presentation as well as being important in several autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus. Due to its protein stabilising properties, increased HSC70 could contribute to enhanced self-antigen collection and presentation and thereby contribute to the development of Type 1 diabetes.

Ort, förlag, år, upplaga, sidor
Taylor & Francis, 2022
Nyckelord
B lymphocyte, HSC70, immune complex, NOD mouse, Type 1 diabetes
Nationell ämneskategori
Immunologi inom det medicinska området
Forskningsämne
immunologi
Identifikatorer
urn:nbn:se:umu:diva-199900 (URN)10.1080/08916934.2022.2117307 (DOI)000855330200001 ()36120986 (PubMedID)2-s2.0-85138421853 (Scopus ID)
Forskningsfinansiär
DiabetesfondenBarndiabetesfonden
Tillgänglig från: 2022-10-03 Skapad: 2022-10-03 Senast uppdaterad: 2022-11-29Bibliografiskt granskad
Lejon, K., Hellman, U., Do, L., Kumar, A. & Forsblad-d'Elia, H. (2022). Increased proportions of inflammatory T cells and their correlations with cytokines and clinical parameters in patients with ankylosing spondylitis from northern Sweden. Scandinavian Journal of Immunology, 96(3), Article ID e13190.
Öppna denna publikation i ny flik eller fönster >>Increased proportions of inflammatory T cells and their correlations with cytokines and clinical parameters in patients with ankylosing spondylitis from northern Sweden
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2022 (Engelska)Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 96, nr 3, artikel-id e13190Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Ankylosing spondylitis (AS) is an autoimmune disease affecting parts of the skeletal structure in particular. Previously increased levels of the inflammatory cell types Th17, Th22, Tc17 and Tc22 cells have been shown to be associated with AS. Here, we analysed the levels of inflammatory T cell subsets, related cytokines and clinical characteristics of AS patients vs controls from northern Sweden. Peripheral blood mononuclear cells (PBMCs) obtained from 50 AS patients and 50 matched controls were short term stimulated with PMA/Ionomycin, stained and analysed by flow cytometry. Plasma levels of Interleukin (IL)-17, IL-22, IL-10 as well as clinically relevant markers were determined. Compared to male controls, male AS patients showed 1.5- to 2-fold increases of Th17 (P = .013), Th22 (P = .003) and Tc22 (P = .024) among CD45+CD3+ lymphocytes. Plasma IL-22 levels correlated with the Tc17 proportion in male patients (Rs = 0.499, P = .003) and plasma IL-10 levels were inversely correlated with Tc17 among all patients (Rs = −0.276, P = .05). Male patients with syndesmophytes showed significantly higher Th17 proportions (P = .038). In female AS patients, Tc22 was negatively correlated with C-reactive protein (high sensitivity) (hsCRP) (Rs = −0.573, P = .016). We confirmed increased proportions of inflammatory T cells and correlations with relevant cytokines from male AS patients. The correlation between Th17 and syndesmophytes supports a role of Th17 in the pathogenic process.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2022
Nyckelord
ankylosing spondylitis, radiographic axial spondyloarthritis, T cells
Nationell ämneskategori
Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-196537 (URN)10.1111/sji.13190 (DOI)000804576100001 ()35506752 (PubMedID)2-s2.0-85131064416 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2016‐02035Region Västerbotten, ALFVLL‐640251Stiftelsen Konung Gustaf V:s 80-årsfond, FAI‐2017‐0454Reumatikerförbundet
Tillgänglig från: 2022-06-14 Skapad: 2022-06-14 Senast uppdaterad: 2022-11-29Bibliografiskt granskad
Do, L., Granåsen, G., Hellman, U., Lejon, K., Geijer, M., Baraliakos, X., . . . Forsblad-d'Elia, H. (2021). Anti-CD74 IgA autoantibodies in radiographic axial spondyloarthritis: a longitudinal Swedish study. Rheumatology, 60(9), 4085-4093
Öppna denna publikation i ny flik eller fönster >>Anti-CD74 IgA autoantibodies in radiographic axial spondyloarthritis: a longitudinal Swedish study
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2021 (Engelska)Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 60, nr 9, s. 4085-4093Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVES: Antibodies against anti-CD74 are related to axial spondyloarthritis (axSpA). The objectives were (i) to study IgA anti-CD74 in radiographic (r)-axSpA patients in the Backbone cohort and to calculate the sensitivity and specificity of anti-CD74, (ii) to study the fluctuation of IgA anti-CD74 levels in prospectively collected samples, and (iii) to explore the relation between IgA anti-CD74 and radiographic spinal changes.

METHODS: IgA anti-CD74 was analysed by ELISA in 155 patients with r-axSpA and age- and sex-matched controls. BASDAI, ASDAS, BASFI and BASMI were assessed and spinal radiographs were scored for r-axSpA-related changes with mSASSS. Previously donated samples, before inclusion in the Backbone study, were identified in the Medical Biobank of Northern Sweden.

RESULTS: A total of 155 patients comprising 69% men and 31% women, age [mean (s.d.)] 55.5 (11.4) years and 152 (98.1%) HLA-B27 positive, were included. The plasma level of IgA anti-CD74 was significantly higher in the patients [median (interquartile range), 12.9 (7.9-17.9) U/ml] compared with controls [10.9 (7.2-14.6) U/ml, P = 0.003]. IgA anti-CD74 was above the cut-off level of 20 U/ml in 36/155 (23.2%) patients and in 15/151 (9.9%) controls (P = 0.002). Multivariable logistic regression analyses revealed ≥1 syndesmophyte associated with IgA anti-CD74 (odds ratio 5.64; 95% CI: 1.02, 35.58; P = 0.048) adjusted for hsCRP, smoking, BMI, sex and age. No distinct pattern of IgA anti-CD74 over time was revealed.

CONCLUSION: Plasma levels of IgA anti-CD74 were increased in r-axSpA and independently associated with radiographic spinal changes, which suggests that IgA anti-CD74 could play a role in the pathogenies of r-axSpA.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2021
Nyckelord
IgA anti-CD74, outcomes research, radiographic axial spondyloarthritis ankylosing spondylitis
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-191231 (URN)10.1093/rheumatology/keaa882 (DOI)000710982100036 ()33369649 (PubMedID)2-s2.0-85114422689 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2016-02035Region Västerbotten, ALFVLL-640251Stiftelsen Konung Gustaf V:s 80-årsfond, FAI-2017-0454
Tillgänglig från: 2022-01-17 Skapad: 2022-01-17 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
Wahlin, B., Fasth, A., Karp, K., Lejon, K., Malmström, V., Rahbar, A., . . . Södergren, A. (2021). Atherosclerosis in rheumatoid arthritis: associations between anti-cytomegalovirus IgG antibodies, CD4+CD28null T-cells, CD8+CD28null T-cells and intima-media thickness. Clinical and Experimental Rheumatology, 39(3), 578-586
Öppna denna publikation i ny flik eller fönster >>Atherosclerosis in rheumatoid arthritis: associations between anti-cytomegalovirus IgG antibodies, CD4+CD28null T-cells, CD8+CD28null T-cells and intima-media thickness
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2021 (Engelska)Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 39, nr 3, s. 578-586Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objectives: Patients with rheumatoid arthritis (RA) have an accelerated progression of atherosclerosis. The aims of this study were to study the associations between subsets of T-cells, subclinical atherosclerosis assessed by intima-media thickness (IMT) and serological status for CMV in patients with RA.

Methods: Patients with new-onset RA (n=79), aged ≤60 years at diagnosis, were included in a prospective study of atherosclerosis. Controls matched for age and sex were also included (n=44). Ultrasound measurement of IMT in the common carotid artery was undertaken at inclusion (T0), after 1.5 years (T1.5) and after 11 years (T11). At T11, flow-cytometry analysis was undertaken to investigate subsets of T-cells. Serological analysis for CMV was undertaken from samples collected at T0.

Results: At T0, 66% of the patients and controls were CMV immunoglobulin G-positive. CMV-IgG positive patients had a significantly more rapid increase in IMT at T1.5, compared with controls and CMV-IgG negative patients. CMV-IgG positive patients had a significantly higher percentage of T-cells lacking CD28 (both CD4+CD28null and CD8+CD28null T-cells) than CMV-IgG negative patients. Increased levels of CD4+CD28null and CD8+CD28null T-cells were significantly associated with IMT at T11, adjusted for systolic blood pressure. CX3CR1 was expressed in CD4+ and CD8+ CD28null T-cells, but CX3CR1 per se was not associated with increased IMT.

Conclusions: Presence of CMV IgG-antibodies in patients with RA is associated with altered T-cell-populations and an increased burden of atherosclerosis. A possible protective effect of antiviral treatment in CMV-positive patients with new-onset RA should be considered.

Ort, förlag, år, upplaga, sidor
Clinical and Experimental Rheumatology S.A.S., 2021
Nyckelord
rheumatoid arthritis, atherosclerosis, T-cells, CD28, cytomegalovirus
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-158135 (URN)10.55563/clinexprheumatol/gs3o43 (DOI)32896254 (PubMedID)2-s2.0-85106505647 (Scopus ID)
Forskningsfinansiär
Region VästerbottenStiftelsen Konung Gustaf V:s 80-årsfondReumatikerförbundet
Anmärkning

Previously included in thesis in manuscript form. 

Tillgänglig från: 2019-04-12 Skapad: 2019-04-12 Senast uppdaterad: 2023-12-04Bibliografiskt granskad
Forsblad-D'elia, H., Hellman, U., Kumar, A. & Lejon, K. (2021). DECREASED LEVELS OF T FOLLICULAR HELPER (CD4+CXCR5+) CELLS AND CD27+CD38+ AND CD27+CD38- B CELLS IN ANKYLOSING SPONDYLITIS PATIENTS CORRELATE WITH MARKER OF INFLAMMATION. Annals of the Rheumatic Diseases, 80(Suppl 1), 13-14, Article ID OP0024.
Öppna denna publikation i ny flik eller fönster >>DECREASED LEVELS OF T FOLLICULAR HELPER (CD4+CXCR5+) CELLS AND CD27+CD38+ AND CD27+CD38- B CELLS IN ANKYLOSING SPONDYLITIS PATIENTS CORRELATE WITH MARKER OF INFLAMMATION
2021 (Engelska)Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 80, nr Suppl 1, s. 13-14, artikel-id OP0024Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Ort, förlag, år, upplaga, sidor
BMJ Publishing Group Ltd, 2021
Nationell ämneskategori
Immunologi inom det medicinska området Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-188046 (URN)10.1136/annrheumdis-2021-eular.785 (DOI)000692629300024 ()
Tillgänglig från: 2021-10-11 Skapad: 2021-10-11 Senast uppdaterad: 2022-10-03Bibliografiskt granskad
Renman, E., Brink, M., Ärlestig, L., Rantapää-Dahlqvist, S. & Lejon, K. (2021). Dysregulated microRNA expression in rheumatoid arthritis families-a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls. Clinical Rheumatology, 40(6), 2387-2394
Öppna denna publikation i ny flik eller fönster >>Dysregulated microRNA expression in rheumatoid arthritis families-a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls
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2021 (Engelska)Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 40, nr 6, s. 2387-2394Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVE: Recent studies have demonstrated an altered expression of certain microRNAs in patients with rheumatoid arthritis (RA) as well as their first-degree relatives (FDRs) compared to healthy controls (HCs), suggesting a role of microRNA in the progression of the disease. To corroborate this, a set of well-characterized RA families originating from northern Sweden were analyzed for differential expression of a selected set of microRNAs.

METHOD: MicroRNA was isolated from frozen peripheral blood cells obtained from 21 different families and included 26 RA patients, 22 FDRs, and 21 HCs. Expression of the selected microRNAs miR-22-3p, miR-26b-5p, miR-34a-3p, miR-103a-3p, miR-142-3p, miR-146a-5p, miR-155, miR-346, and miR-451a was determined by a two-step quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis including clinical variables was applied.

RESULTS: Out of the nine selected microRNAs that previously have been linked to RA, we confirmed four after adjusting for age and gender, i.e., miR-22-3p (p = 0.020), miR-26b-5p (p = 0.018), miR-142-3p (p = 0.005), and miR-155 (p = 0.033). Moreover, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs. In addition, analysis of the effect of corticosteroid use showed modulation of miR-103a-3p expression.

CONCLUSIONS: We confirm that microRNAs seem to be involved in the development of RA, and that the expression pattern in FDR is partly overlapping with RA patients. The contribution of single microRNAs in relation to the complex network including all microRNAs and other molecules is still to be revealed. Key Points • Expression levels of miR-22-3p, miR-26b-5p, miR-142-3p, and miR-155 were significantly altered in RA patients compared to those in controls. • In first-degree relatives, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs.

Ort, förlag, år, upplaga, sidor
Springer, 2021
Nyckelord
Autoimmunity, MicroRNA family, Rheumatoid arthritis, Sweden
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-176964 (URN)10.1007/s10067-020-05502-9 (DOI)000591447600001 ()33210166 (PubMedID)2-s2.0-85096216498 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 201802551Konung Gustaf V:s JubileumsfondReumatikerförbundet
Tillgänglig från: 2020-11-23 Skapad: 2020-11-23 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Lejon, K., Hellman, U., Do, L., Kumar, A. & Forsblad-d'Elia, H. (2020). Increased Proportion of TH17, TH22 and TC17 Cells and the Correlation to IL-22 and Clinical Parameters in Patients with Ankylosing Spondylitis from Northern Sweden. Paper presented at ACR Convergence 2020, Virtual, November 5-9, 2020. Arthritis & Rheumatology, 72, Article ID 1858.
Öppna denna publikation i ny flik eller fönster >>Increased Proportion of TH17, TH22 and TC17 Cells and the Correlation to IL-22 and Clinical Parameters in Patients with Ankylosing Spondylitis from Northern Sweden
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2020 (Engelska)Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 72, artikel-id 1858Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Abstract [en]

Background/Purpose: Increased levels of TH17 and TH22 as well as TC17 and TC22 cells have previously been associated with ankylosing spondylitis (AS). The correlation between these inflammatory T cell subsets and clinically relevant parameters as well as cytokines has also been reported. However, the status of these inflammatory cells in a well characterized AS cohort from northern Sweden has not been studied. The purpose of this study was to confirm the increased presence of inflammatory T cell subsets in peripheral blood of patients with AS from northern Sweden in relation to age and sex-matched controls. In addition, associations of clinically relevant parameters with the level of the inflammatory T cell subset(s) and cytokines of interest were performed.

Methods: Peripheral blood mononuclear cells (PBMCs) from a cohort of 50 patients with AS from Region Västerbotten (Modif NY, mean age 52±9.1 years, 33 (66 %) men, 50 (100 %) HLAB27) and 50 pair wise matched blood donor controls (mean age 54±8.8 years, 33 (66 %) men) were stained with a combination of antibodies allowing for the detection of surface expressed CD45, CD3, CD4, CD8, intracellular IL-17 and IL-22 and analyzed by flow cytometry. In addition, levels of IL-17 and IL-22 in plasma were determined by the Meso Scale Discovery platform. The patient with AS were examined with spinal x-ray for radiographic alterations assessed with mSASSS. CRP and ESR were measured and physical function and disease activity were registered with BASMI and BASFI respectively ASDAS-CRP and BASDAI.

Results: Pair wise comparison of AS patients and controls showed a 1,5 to 2-fold increase of TH17, TH22 and TC22 cells among CD45+CD3+ lymphocytes in PBMCs of male patients (p=0,013, p=0,003 and p=0,024 respectively). Levels of IL-22 in plasma and proportion of TC17 correlated in male patients (Rs=0,499 p=0,003) and plasma levels of IL10 showed an inverse correlation in relation to TC17 in all patients (Rs=-0,276 p=0,05). In female AS patients there was a negative correlation between TC22 and CRP (Rs = -0,573, p=0,016). In addition, after splitting the group of female into pre- and postmenopausal correlation between TC17 and mSASSS (Rs = 0,845, p=0,034), TC22 and BASFI (Rs = 0,986, p=0,0003) (premenopausal) and TC22 and BASMI (Rs = 0,764, p=0,006) (postmenopausal) was observed.

Conclusion: We confirm an increased proportion of TH17, TH22 and TC17 cells in blood in AS male patients from northern Sweden. In addition, positive correlation of the proinflammatory cytokine IL-22 and negative correlation of anti-inflammatory cytokine IL-10 in relation to TC17 corroborate the influence of these cells in the disease process. Interestingly, in female AS patients there was a correlation between clinical relevant parameters to particular inflammatory T cell subset dependent on the menopausal status, suggesting a role of female sex hormones in AS pathogenesis.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2020
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-178547 (URN)10.1002/art.41538 (DOI)000587568506109 ()
Konferens
ACR Convergence 2020, Virtual, November 5-9, 2020
Anmärkning

SESSION INFORMATION:

Date: Monday, November 9, 2020

Session Title: Spondyloarthritis Including Psoriatic Arthritis – Basic Science PosterSession Type: Poster Session D

Tillgänglig från: 2021-01-14 Skapad: 2021-01-14 Senast uppdaterad: 2022-10-03Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-5025-6539

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