Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and associates with HLA-DRB1*04. The Collagen IIp261-273-specific T cell repertoire in the peripheral blood of DR4 + patients at the onset of the disease shows a restricted TCR-beta chain usage among which the most frequent is TRBV25. To define whether this group of DR4-restricted collagen-specific shared T cell could represent markers of active-severe 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 report that the presence of T cells carrying rearrangement TRBV25 associated with HLA-DR haplotype and disease activity. HLA-DRB1* haplotypes 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 DMARDs. Finally, the HLA-DRB1* haplotype appeared complementary with current serologic tools to predict good and poor responders in a treat to target strategy. The data reported here offer clues to predict the course of the disease and to foresee personalized treatments in RA patients.
Keywords: ACPA; ACPA, anti-cyclic citrullinated peptide antibodies; APCs, antigen presenting cells; CDR3, complementarity-determining region 3; CRP, C-reactive protein; Clonotypes; Coll261-273, human collagen derived peptide; DAS, disease activity score; Disease activity; ERA, early rheumatoid arthritis; ESR, erythrocyte sedimentation rate; GWAS, genome wide association studies; HAQ, Health Assessment Questionnaire; HLA, histocompatibility leucocyte antigen; HLA-DRB1; MHC, major histocompatibility complex; PBMC, peripheral blood mononuclear cells; RF, rheumatoid factor; RT-PCR, reverse transcription polymerase chain reaction; SJC, swollen joint count; SNP, single nucleotide polymorphism; TCR, T cell receptor; TJC, tender joint count; TRBJ, junctional beta chain gene of TCR; TRBV 25; TRBV, variable beta chain gene of TCR.