Increased proportions of inflammatory T cells and their correlations with cytokines and clinical parameters in patients with ankylosing spondylitis from northern Sweden

Lejon, Kristina; Hellman, Urban; Do, Lan; Kumar, Akshay; Forsblad-d’Elia, Helena

doi:10.1111/sji.13190

Cited by 9 publications

(8 citation statements)

References 48 publications

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“…In male AS patients, a similar correlation was found for the cytokine IL‐22. We have recently demonstrated that TH22 and TC22 cells were increased in men with AS 15 . IL‐22 has been shown to be linked to autoimmunity in several diseases 44 .…”

Section: Discussionmentioning

confidence: 93%

“…The involvement of inflammatory T cells, such as TH17, TH22; TC17 and TC22 in AS pathogenesis has been demonstrated. 12 , 13 , 14 , 15 In addition, we recently demonstrated, for the first time, an association between higher TH17 levels and the presence of syndesmophytes 15 further emphasizing the role of TH17 cell‐driven inflammation in the effector phase of the disease.…”

Section: Introductionmentioning

confidence: 83%

“…24 Rather, the clear genetic linkage to HLA-B*27 and its strong connection to cell-mediated immunity, 10,11 additional linkage to mainly non-B-cellrelated molecules, 31 as well as the observed correlation of inflammatory TH17 cells and the affiliated cytokines support the involvement of cell-mediated adaptive immune responses in AS pathogenesis. [12][13][14][15] However, in some studies, the role of B cells as contributing players in AS pathology has still been argued for. In the AS lesions infiltrating B cells can be observed 23 and although AS-specific antibodies is still to be revealed there are several examples of increased levels of autoantibodies in AS.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the subtle or no therapeutic impact of B‐cell‐related treatments such as rituximab and related drugs has further supported this notion 24 . Rather, the clear genetic linkage to HLA‐B*27 and its strong connection to cell‐mediated immunity, 10,11 additional linkage to mainly non‐B‐cell‐related molecules, 31 as well as the observed correlation of inflammatory TH17 cells and the affiliated cytokines support the involvement of cell‐mediated adaptive immune responses in AS pathogenesis 12–15 …”

Section: Discussionmentioning

confidence: 99%

“…We have recently demonstrated that TH22 and TC22 cells were increased in men with AS. 15 IL‐22 has been shown to be linked to autoimmunity in several diseases. 44 A more precise mechanism on how this multilayered cytokine network could affect B‐cell numbers is still to be revealed, but our findings suggest that the balance between inflammation and no inflammation could partly depend on this.…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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

et al. 2022

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Immunological biomarkers in patients with radiographic axial spondyloarthritis, an exploratory longitudinal Swedish study

Hellman,

Lejon,

et al. 2024

Modern Rheumatology

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Objectives There is a need for more specific biomarkers to diagnose and predict disease course in patients with axial spondyloarthritis (axSpA). This study aimed to study immunological plasma biomarkers, at different time-points in radiographic (r)-axSpA patients overall and stratified by sex and compare these biomarker pattern in r-axSpA patients concerning disease phenotypes and disease activity. Methods Plasma samples were analysed from r-axSpA patients at and prior (Pre-Backbone) inclusion in the Backbone study. Interferon gamma, interleukin-10, -17A, -17F, -22, -23, -6, MCP-1, TNF-α, VEGF-A, MIF, IgA anti-CD74, zonulin, ESR, hsCRP, white blood cell count, and blood lipids were measured. Results Biomarker pattern discriminated significantly between r-axSpA patients in Backbone and Pre-Backbone compared with controls. When stratifying by sex, it was possible to discriminate between male and female r-axSpA patients in Backbone vs controls and between male r-axSpA patients in pre-Backbone and controls. In Backbone, markers with high discriminative capacity were MIF, IgA anti-CD74, and MCP-1. In Pre-Backbone, IL-6, TNF-α, MIF, triglycerides, cholesterol, IL-10, and zonulin displayed high discriminative capacity. Conclusion Based on their temporal pattern and mutual relationship, we suggest studying MIF, IgA anti-CD74, and MCP-1 in depth, at more time points, to further elucidate disease-driving mechanisms in this complex disease.

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Sex differences in patient-reported outcome measures and the association with clinical factors in axial spondyloarthritis patients treated with tumour necrosis factor inhibitors

Hellamand,

van de Sande,

Nurmohamed

et al. 2024

Rheumatology

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Objectives To investigate sex differences in patient-reported outcome measures (PROMs) among axSpA patients initiating their first TNFi and identify factors contributing to these disparities over the follow-up. Methods Data were included from 15 EuroSpA registries and consisted of axSpA patients initiating their first TNFi, with ≥2 measurements for each analysed PROM (BASDAI and BASFI, scale 0–100) taken at any time point. Linear mixed models were employed to analyse sex differences in PROMs over 24 months and to evaluate how baseline characteristics were related to the observed sex differences. Results We analysed 13 102 (38% women) in the BASDAI analyses and 10 623 (38% women) in the BASFI analyses. At follow-up, mean sex differences in BASDAI increased from 4.3 units at baseline (95% CI, 3.5–5.1)–8.0 (7.2–8.8) at 6 months, and in BASFI from 2.2 (1.4–3.1)–4.6 (3.6–5.5), with consistently worse scores in women. Baseline characteristics could not substantially account for the observed sex differences over time; however, the magnitude of the sex differences was reduced by HLA-B27 positivity, longer disease duration, and increased CRP levels, but increased by TNFi initiation in later years and peripheral arthritis. Conclusion In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA.

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Increased proportions of inflammatory T cells and their correlations with cytokines and clinical parameters in patients with ankylosing spondylitis from northern Sweden

Cited by 9 publications

References 48 publications

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

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

Immunological biomarkers in patients with radiographic axial spondyloarthritis, an exploratory longitudinal Swedish study

Sex differences in patient-reported outcome measures and the association with clinical factors in axial spondyloarthritis patients treated with tumour necrosis factor inhibitors

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