OP0224 Th17 Cells and TFH Cells and their Cytokine Products Are Enriched in the Synovium of Rheumatoid Arthritis Patients and Correlate with Disease Activity

Background:Reactive oxygen species (ROS) and T helper 17 (TH17) cells have been known to play an important role in the pathogenesis of rheumatoid arthritis (RA). However, the interrelationship between ROS and TH17 remains unclear in RAObjectives:To explore whether ROS affect TH17 cells in peripheral blood mononuclear cells (PBMC) of RA patients, we analyzed ROS expressions among T cell subsets following treatment with mitochondrial electron transport chain complex inhibitors.Methods:Blood samples were collected from 40 RA patients and 10 healthy adult volunteers. RA activity was divided according to clinical parameter DAS28. PBMC cells were obtained from the whole blood using lymphocyte separation medium density gradient centrifugation. Following PBMC was stained with Live/Dead stain dye, cells were incubated with antibodies for CD3, CD4, CD8, and CD25. After fixation and permeabilization, samples were stained with antibodies for FoxP3 and IL-17A. MitoSox were used for mitochondrial specific staining.Results:The frequency of TH17 cells was increased by 4.83 folds in moderate disease activity group (5.1>DAS28≥3.2) of RA patients compared to healthy control. Moderate RA activity patients also showed higher ratio of TH17/Treg than healthy control (3.57 folds). All RA patients had elevated expression of mitochondrial specific ROS than healthy control. When PBMC cells were treated with 2.5uM of antimycin A (mitochondrial electron transport chain complex III inhibitor) for 16 h, the frequency of TH17 cells was significantly decreased.Conclusion:The mitochondrial electron transport chain complex III inhibitor markedly downregulated the frequency of TH17 cells in moderate disease activity patients with RA. These findings provide a novel approach to regulate TH17 function in RA through mitochondrial metabolism related ROS production.References:[1]Szekanecz, Z., et al., New insights in synovial angiogenesis. Joint Bone Spine, 2010. 77(1): p. 13-9.[2]Prevoo, M.L., et al., Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum, 1995. 38(1): p. 44-8.Disclosure of Interests:None declared

Download Full-text

The relationship of blood CDC42 level with Th1 cells, Th17 cells, inflammation markers, disease risk/activity, and treatment efficacy of rheumatoid arthritis

Irish Journal of Medical Science (1971 -) ◽

10.1007/s11845-021-02858-y ◽

2021 ◽

Author(s):

Yongji Li ◽

Wendi Yang ◽

Feng Wang

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Treatment Response ◽

Treatment Efficacy ◽

Th17 Cells ◽

Immune Cell ◽

Disease Risk ◽

Th1 Cells ◽

Clinical Role ◽

Reactive Protein

Abstract Background Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. Methods After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. Results Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. Conclusion CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

Download Full-text

B cell depletion treatment decreases Th17 cells in patients with rheumatoid arthritis

10.21203/rs.3.rs-408266/v1 ◽

2021 ◽

Author(s):

Constantina A. Bounia ◽

Stamatis-Nick C Liossis

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

B Cell ◽

Th17 Cell ◽

Th17 Cells ◽

Treg Cells ◽

Cell Depletion ◽

B Cell Depletion ◽

Das28 Score ◽

Autoimmune Rheumatic Diseases

Abstract Introduction: We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA).Patients and methods: We analyzed 16 patients with RA initiating RTX treatment, 11 patients with RA initiating abatacept treatment, 11 patients with RA treated with other medications, 8 patients with other autoimmune rheumatic diseases initiating RTX, and 14 healthy volunteers. Th17 cells (CD4+IL23R+IL17A+) and Treg cells (CD4+CD25hiFoxP3+) were evaluated flow-cytometrically.Results: Th17 cells from patients treated with RTX decreased significantly at weeks 8 and 16 (mean ± SEΜ: 3.01% ± 0.54℅ CD4+ cells at week 0 vs. 1.53% ± 0.24℅ at week 8 vs 1.10% ± 0.20℅ at week 16, p = 0.0004). Reductions of Th17 cells were evident in:clinical responders (DAS28 score ≤ 3.2), ACPA (+) and RF (-) patients; circulating Tregs remained stable. Th17 and Tregs were not affected by ABA treatment or by changes in disease activity. Tregs, but not Th17 cells, decreased following treatment with RTX in patients with other autoimmune diseases (0.75% ± 0.16% at week 0 vs. 0.43% ± 0.16% at week 8, p = 0.033).Conclusion: RTX-induced B cell depletion results in a significant reduction of circulating Th17 cell percentages, whereas it has no effect on Tregs of patients with RA. This reduction of Th17 cells was evident particularly in responders to RTX treatment, ACPA+ and RF (-) patients with RA.

Download Full-text

Analysis of CXCR5+Th17 cells in relation to disease activity and TNF inhibitor therapy in Rheumatoid Arthritis

Scientific Reports ◽

10.1038/srep39474 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 9

Author(s):

Deepika Singh ◽

Matthew Henkel ◽

Bernadette Sendon ◽

June Feng ◽

Anthony Fabio ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Th17 Cells ◽

Inhibitor Therapy ◽

Tnf Inhibitor

Download Full-text

Are Joint-associated Th17 Cells Related to Disease Activity in Rheumatoid Arthritis?

Clinical Immunology ◽

10.1016/j.clim.2010.03.131 ◽

2010 ◽

Vol 135 ◽

pp. S43

Author(s):

Nicola Gullick ◽

Hayley Evans ◽

David Jayaraj ◽

Bruce Kirkham ◽

Leonie Taams

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Th17 Cells

Download Full-text

B Cell Depletion Therapy Normalizes Circulating Follicular Th Cells in Primary Sjögren Syndrome

The Journal of Rheumatology ◽

10.3899/jrheum.160313 ◽

2016 ◽

Vol 44 (1) ◽

pp. 49-58 ◽

Cited By ~ 29

Author(s):

Gwenny M. Verstappen ◽

Frans G.M. Kroese ◽

Petra M. Meiners ◽

Odilia B. Corneth ◽

Minke G. Huitema ◽

...

Keyword(s):

T Cell ◽

Disease Activity ◽

B Cell ◽

Th17 Cells ◽

Serum Levels ◽

Cd4 T Cell ◽

Cell Depletion ◽

B Cell Depletion ◽

Tfh Cells ◽

Primary Sjögren Syndrome

Objective.To assess the effect of B cell depletion therapy on effector CD4+ T cell homeostasis and its relation to objective measures of disease activity in patients with primary Sjögren syndrome (pSS).Methods.Twenty-four patients with pSS treated with rituximab (RTX) and 24 healthy controls (HC) were included. Frequencies of circulating effector CD4+ T cell subsets were examined by flow cytometry at baseline and 16, 24, 36, and 48 weeks after the first RTX infusion. Th1, Th2, follicular Th (TFH), and Th17 cells were discerned based on surface marker expression patterns. Additionally, intracellular cytokine staining was performed for interferon-γ, interleukin (IL)-4, IL-21, and IL-17 and serum levels of these cytokines were analyzed.Results.In patients with pSS, frequencies of circulating TFH cells and Th17 cells were increased at baseline compared with HC, whereas frequencies of Th1 and Th2 cells were unchanged. B cell depletion therapy resulted in a pronounced decrease in circulating TFH cells, whereas Th17 cells were only slightly lowered. Frequencies of IL-21–producing and IL-17–producing CD4+ T cells and serum levels of IL-21 and IL-17 were also reduced. Importantly, the decrease in circulating TFH cells was associated with lower systemic disease activity over time, as measured by the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index scores and serum IgG levels.Conclusion.B cell depletion therapy in patients with pSS results in normalization of the elevated levels of circulating TFH cells. This reduction is associated with improved objective clinical disease activity measures. Our observations illustrate the pivotal role of the crosstalk between B cells and TFH cells in the pathogenesis of pSS.

Download Full-text

Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondyloarthritis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.107649 ◽

2009 ◽

Vol 69 (3) ◽

pp. 618-623 ◽

Cited By ~ 94

Author(s):

Lode Melis ◽

Bernard Vandooren ◽

Elli Kruithof ◽

Peggy Jacques ◽

Martine De Vos ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Th17 Cells ◽

Differential Regulation ◽

Effector T Cell ◽

Inflammatory Conditions ◽

Gene Coding ◽

Local Parameters ◽

Th17 Cytokine

ObjectivesTh17 cells are an effector T-cell population that plays a role in chronic inflammatory conditions and is dependent on IL-23 for their survival and expansion. More recently, a genetic association was discovered between polymorphisms in the gene coding for the IL-23 receptor and spondyloarthritis. This study aimed to evaluate the role of Th17-associated cytokines in spondyloarthritis pathogenesis by measuring their levels in the joints and circulation as well as correlating them with disease activity parameters.MethodsPaired synovial fluid (SF), serum and synovial biopsies were obtained from 30 non-PsA (psoriatic arthritis) spondyloarthritis, 22 PsA and 22 rheumatoid arthritis (RA) patients. IL-17, IL-23 and CCL20 were measured by ELISA in the SF and serum of patients and correlated with systemic and local parameters of disease activity.ResultsConcentrations of CCL20, a major Th17-attracting chemokine, tended to be higher in the joints of RA than in spondyloarthritis patients. Interestingly, levels of CCL20 were markedly higher in SF as opposed to serum. In addition, there was a remarkable association between the expression of the Th17 cytokine system and the presence of intimal lining layer hyperplasia in RA. Also in the serum, there was a tendency for higher IL-23 levels in RA, which correlated strongly with disease activity parameters.ConclusionsTh17-related cytokines are expressed in joints of spondyloarthritis as well as RA patients. IL-23 levels, however, correlate with disease activity parameters in RA only. These results point towards a differential regulation of the Th17 cytokine system in spondyloarthritis compared with RA.

Download Full-text