Collagen specific T-cell repertoire in DR4+ patients identifies new biomarkers in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and associates with HLA-DRB1*04. The Collagen II261-273-specific T cells repertoire in the peripheral blood of DR4+ patients at the onset of the disease shows a restricted TCR-beta chain usage. The two TCR-beta chains used more frequently are TRBV25 and TRBV6_4. To define whether this group of DR4-retricted collagen-specific T cell could represent new markers of severity of the disease and response to therapy, 90 subjects affected by early-RA were enrolled in the study; peripheral blood mononuclear cells were cultured with or without the human collagen II peptide p261-273 and were examined by immunoscope analysis for the usage of the previously identified shared TCR-beta chains. We also studied the secretion of IL-17 and IL-13 by collagen-specific individual T cells in 2 of the DR4+ patients.We report that the presence of T cells carrying rearrangements TRBV25 and TRBV6_4 was correlated to HLA-DR and disease activity; the detection of the TRBV25 T cells could predict the active disease in DR4+ patients. HLA-DRB1* allele combinations 04/04, 04/01 and 04/11 were significantly associated with usage of TRBV25, higher disease activity at the onset of disease and poor response to DMARD. The data reported here offer clues to predict the course of the disease and to foresee personalized treatments in RA patients.