Background/Purpose: More than 50% of people with new-onset RA may achieve remission within the first year on conventional synthetic (cs)-DMARDs. Sustained remission confers better long-term outcomes, including a greater potential to stop treatment. To understand the state of autoreactive T cells associated with remission and the potential for this restored immune tolerance, we compared the trajectory of changes in CD4+ autoreactive T cells recognising citrullinated (cit)-vimentin in RA patients achieving remission or not at 6 months post-onset.

Methods: Fifteen drug-naïve HLA-DRB1*04:01, *01:01 or *04:04⁺ RA patients were recruited within 3 months of diagnosis to the Australian Autoimmune Arthritis Biobank Collaborative (A3BC), and treated with methotrexate, hydroxychloroquine, sulfasalazine and leflunomide, singly or in combination. They were followed for at least 6 months, and up to 24 months. Disease activity scores (DAS) and PBMC were collected at baseline, 6, 12 and 24 months. At 6 months, remission was defined as DAS28-CRP< 2.4. PBMC were assessed using a 17-marker spectral flow panel, incorporating HLA-DRB1*04:01/01:01-VimentinCit64_59-71 or HLA-DRB1*04:04-VimentinCit71_66-78 tetramers. Changes in the number of cit-vimentin-specific cell subsets over time were assessed using a generalized linear mixed model with a negative binomial distribution, while differences in paired remission/non-remission group comparisons used the Wilcoxon signed-rank test.

Results: The mean age at disease onset was 59.1 years (SD 13.6). Twelve of the 15 were ACPA+, 11 RF+ and 10 ACPA+RF+. Eleven of 15 (72.7% ACPA+) achieved remission at 6 months. At baseline, relative to the total CD4+ population, the cit-vimentin-specific CD4+ T cells were enriched in CXCR5+PD1+ follicular helper (Tfh), CXCR5-PD1+ peripheral helper (Tph), CXCR3+CCR4+ memory, CD39+ T cell and CD25+CD127- Treg phenotypes, and depleted in naïve and CD39+Treg phenotypes. When comparing trajectories over 12 months, cit-vimentin-specific CD4+ Treg and Tfh were differentially expressed, with a steeper reduction in Tfh in patients achieving remission than non-remission by 6 months. These changes were not observed in total CD4+ T cells. By 6 and 12 months, cit-vimentin-specific T cells were no longer enriched in Tfh, Tph, CXCR3+CCR4+ memory or depleted in Treg relative to CD4+ T cells.

Conclusion: In early RA, peripheral blood cit-vimentin-specific T cells are enriched in memory T cells with effector, helper and regulatory phenotypes, but depleted in CD39+ effector Treg. The differential changes in cit-vimentin-specific Tfh and Treg in DMARD-induced remission underscore the importance of rapid modulation of antigen-specific T-cell help for ACPA+ B cells to achieve a remission outcome.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/depletion-of-citrullinated-vimentin-reactive-follicular-helper-t-cells-with-treatment-induced-remission-of-recent-onset-rheumatoid-arthritis-when-compared-to-non-remission-at-6-months/