Session Title: T-cell Biology in Autoimmune Diseases
Session Type: Abstract Submissions (ACR)
Background/Purpose: Improved understanding of the immune events discriminating between seropositive arthralgia and clinical synovitis is of key importance in rheumatology research. Ample evidence suggests a role for Th17 cells in rheumatoid arthritis (RA). We hypothesized that CD4+CD161+ T-cells representing Th17 lineage cells may be modulated prior to or after development of clinical synovitis. Therefore, in a cross-sectional study, we investigated the occurrence of CD4+CD161+ T-cells in seropositive arthralgia patients who are at risk for developing RA and in newly diagnosed RA patients. In a prospective study, we evaluated the effect of methotrexate treatment on circulating CD4+CD161+ T-cells. Next, we assessed if these cells can be detected at the level of the RA joints.
Methods: Whole blood from healthy controls (n=20), ACPA and/or RF seropositive arthralgia patients (n=26) and newly diagnosed, DMARD-free RA patients (n=35), was analyzed by flow-cytometry using anti-CD4, -CD8, -CD45RO, -CCR7, -CD161 fluorochrome-conjugated antibodies. Next, CD4+CD161+ T-cells were prospectively assessed in 26 and 12 RA patients at 3 and 6 months after MTX treatment, respectively. Paired samples (peripheral blood and synovial fluid, n=11) and enzyme-digested synovial tissue cells (n=4) from late-stage RA patients were analyzed for the same markers. T-cell cytokine production potency (IL-17, IFNγ and TNFα) was assessed in peripheral blood mononuclear cells and in synovial fluid mononuclear cells.
Results: Precursor Th17 lineage cells were found to be increased in seropositive arthralgia patients. In contrast, circulating CD161+CD4+ T-cells were decreased in newly diagnosed RA patients. The decrease in CD4+CD161+ T-cells correlated inversely with C-reactive protein (r = -0,43 and p = 0.02) and with the swollen joint count 66 (r = -0,41 and p = 0.03). Methotrexate treatment led to normalization of CD4+CD161+ T-cells and reduced disease activity. CD4+CD161+ T cells were readily detected in synovial tissue from both early and late stage rheumatoid arthritis. In addition, synovial fluid was found to be enriched for CD4+CD161+ T-cells compared to blood. Late stage synovial fluid CD4+CD161+ T-cells showed skewing towards the Th1 phenotype as evidenced by increased IFN-γ expression.
Conclusion: The changes in peripheral numbers of CD4+CD161+ T-cells in seropositive arthralgia and early RA and the enrichment of these cells at the level of the joint predict a role for CD4+CD161+ T-cells in the early immune events leading to clinical synovitis. Our findings may add to the development of RA prediction models and provide opportunities for early intervention.
B. J. Kroesen,
K. S. M. van der Geest,
M. G. Huitema,
W. H. Abdulahad,
A. M. H. Boots,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-cd4cd161-t-lymphocytes-are-increased-in-seropositive-arthralgia-patients-but-decreased-in-patients-with-newly-diagnosed-rheumatoid-arthritis/