Background Recent work has shown that systemic autoimmunity precedes inflammation of the synovium of rheumatoid arthritis (RA) patients. Therefore, we analyzed different T cell subsets in lymph node biopsies obtained during the earliest phases of RA to determine their possible contribution to the inflammatory process.
Objectives To examine the phenotype and functional characteristics of lymph node T cells during different phases of RA.
Methods Seven individuals with arthralgia but without any evidence of arthritis upon physical examination who were positive for IgM rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA; RA risk group) and 7 RA patients (disease duration less than 1 year, naïve for disease-modifying antirheumatic drugs and biologics) were included in the study. All study subjects underwent ultrasound-guided inguinal lymph node biopsy. T-helper (Th)1, cytotoxic T cell (Tc)1, Th2, Tc2, Th17, Tc17 and regulatory T cells (Treg) were analysed by multi-color flow cytometry. Cytokine profiles were determined after stimulation with Phorbol Myristate Acetate (PMA) and Ionomycin in the presence of Brefeldin A and Golgi Stop. We used directly labelled antibodies for CD45, CD3, CD4, CD8, IFN-y (Th1/Tc1), IL-4 (Th2/Tc2), IL-17A (Th17/Tc17), foxp3, and IL-10 (Treg).
Results The number of IFNy or IL-4 producing CD4+ and CD8+ T cells were on average comparable between the RA risk and early arthritis group. An increase of IL-17A producing CD4 T cells (Th17; p=0.04) and IL-10 producing CD4 T cells (p=0.014) could be observed in the early arthritis group compared to the RA risk group. Interestingly, a significant correlation between ACPA titers and IL-10 producing and IL-17A producing CD4 T cells (r=0.78; p=0.0016 and r=0.54; p=0.048) and between IgM-RF and IL-17A producing CD4 T cells (r=0.57; p=0.04) was found when combining both study groups. Additionally, within the RA risk group the levels of IL-10 producing CD4 T cells correlated significantly with the total tender joint count (TOTTJC28; r=0.8697; p=0.03).
Conclusions Flow cytometry analysis of lymph node cells suggests an increase in IL-17A and IL-10 producing CD4 T cells in patients with early RA. Moreover, the number of these T cells correlates with autoantibody levels suggesting an important role of these T cells in the humoral autoimmune response. These data indicate that both proinflammatory cytokines as well as regulatory cytokines are increased during the earliest phases of arthritis, suggesting an early change in the immunoregulatory balance. These results provide for the first time new insights in immunological lymph node changes associated with RA pathogenesis.
Disclosure of Interest None Declared
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