Lightning & Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2026

Autoreactive PD1⁺, TIGIT⁺ CD4⁺ T cells and CD4+ TemRA in peripheral blood predict remission outcomes in response to disease-modifying antirheumatic drugs in early rheumatoid arthritis (#14)

Jia Yi Hee 1 , Hanno Nel 1 , Oxana Radetskaya 1 , Yann Abraham 2 , Carl Coyle 3 , Katrina Chakradeo 1 , Michelle Roch 1 , Mihir Wechalekar 4 , Tom Lynch 5 , Lyn March 5 , Ranjeny Thomas 1
  1. Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
  2. Deeplife, Vernon, France
  3. Centre for Rheumatic Diseases, King’s College London, London, United Kingdom
  4. Rheumatology Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
  5. Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia

Introduction

Approximately 50% of patients with new-onset rheumatoid arthritis (RA) do not achieve remission within the first year on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). Early and sustained remission confers better long-term outcomes, including a greater potential to stop treatment. Anti-citrullinated protein antibodies (ACPA) reactivity includes citrullinated (Cit)-vimentin epitopes, in particular Vimentin59-71Cit64 and Vimentin66-78Cit71, which are T cell epitopes presented by HLA-DR molecules of B cells and other antigen-presenting cells.

Methods

Twenty-one drug-naïve new-onset HLA-DRB1*04:01, *01:01 or *04:04+ RA patients recruited into the Australian Autoimmune Arthritis Biobank Collaborative were treated with methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide, singly or in combination. Disease activity scores using 28 joint counts and C-reactive protein (DAS28-CRP) and peripheral blood mononuclear cells (PBMCs) were collected at baseline, 6, 12 and 24 months. Stable remission was defined as DAS28-CRP<2.4 at 6 and 12 months, slow/intermittent remission as DAS28-CRP≥2.4 at either 6 or 12 months, and non-remission as DAS28-CRP≥2.4 at both 6 and 12 months. PBMCs were assessed using a 17-marker spectral flow panel, including HLA-DRB1*04:01/01:01-Vimentin59-71Cit64 or HLA-DRB1*04:04-Vimentin66-78Cit71 tetramers, and clustered using both supervised and non-supervised methods. Changes in the number of T cell subsets over time between 4 groups; remission samples from stable remission and slow/intermittent remission patients, and low and moderate/high disease activity samples from all patients, were assessed using a generalized linear mixed model with a negative binomial distribution.

Results

Of 21 patients (85.7% ACPA+), 11 achieved stable remission, 7 intermittent remission, and 3 did not achieve remission. CD4⁺ CXCR5-PD1+ Tph, including citrullinated-vimentin-specific CD4⁺ CXCR5-PD1+ Tph, CD4⁺ CCR7+CXCR5-PD1+ Stem-like Tph, CD4⁺ PD1⁺TIGIT⁺ T cells and CD4⁺ TIGIT⁺ T cells were increased with moderate/high disease activity, while citrullinated-vimentin-specific CD4⁺GPR56+CD45RA+CCR7- TemRA, were decreased with low and moderate/high disease activity, as compared to remission in stable remission patients, at baseline. Biplot analysis identified these populations as key determinants distinguishing response groups at 6 and 12 months.

Conclusion

Baseline frequencies of CD4⁺ Tph, stem-like Tph, including those recognizing citrullinated vimentin, are negatively associated with stable remission trajectory, while CD4+ TemRA expressing the GPR56 marker of cytotoxicity are positively associated with stable remission trajectory, in csDMARD-treated recent-onset RA patients. These data suggest that CD4+ helper T cells promote B cells activation, while cytotoxic CD4+ TemRA kills B cells presenting Cit-vimentin in RA to prevent or support remission on csDMARDs.