Participants who later develop rheumatoid arthritis may exhibit significantly lower frequencies of circulating autoreactive T cells in the preclinical phase, according to a recent study.
In the study, published in RMD Open, researchers investigated the role of autoreactive CD4-positive T cells in the preclinical phase of rheumatoid arthritis (RA). The researchers analyzed 20 participants, all of whom had musculoskeletal complaints without clinical or ultrasound evidence of synovitis, who were positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies and HLA-DRB1*04:01. Among the participants, 10 of them progressed to arthritis (progressors) within a median of 13 months, whereas the remainder (nonprogressors) remained arthritis-free over a median follow-up of 53 months.
The study employed HLA-class II tetramer staining and spectral flow cytometry to characterize citrulline-specific CD4-positive T cells. Progressors exhibited significantly lower frequencies of these autoreactive T cells at baseline compared with nonprogressors (P < .05). Citrullinated tenascin–C-specific T cells were the most common autoreactive T cells identified in both groups, though their levels decreased as progressors approached the onset of arthritis. Increased expression of PD-1 and CD95 on memory citrullinated tenascin–C-specific T cells in progressors indicated repeated antigen exposure.
Among the key findings were:
- Progressors had broader antibody reactivity to citrullinated peptides (median six specificities) compared with nonprogressors (median 1.5 specificities).
- The frequency of citrullinated tenascin–C-specific T cells decreased significantly at arthritis onset (P < .05).
- Anti-CCP titers were higher in progressors, aligning with greater disease risk.
The findings reported decreased circulating autoreactive T cells during the at-risk phase of RA, identifying citrullinated tenascin–C-specific T cells as the most frequently observed in progressors and highlighting their potential role in disease development.
Full disclosures can be found in the published study.