We measured proliferative responses to these two peptides in another cohort of patients with RA or osteoarthritis: positive responses were found in 28% of RA, but also in 11% of osteoarthritis patients and these responses could be blocked by anti-MHC class II Ab. Remarkably, the presence of 117/120–133-specific T cells was significantly associated with active disease in RA patients, and bone

Silmitasertib datasheet erosion appeared to be more common in T-cell positive patients. These data suggest involvement of hnRNP-A2 specific cellular autoimmune responses in RA pathogenesis. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by chronic synovial inflammation in multiple joints leading to cartilage and bone damage and disability. The prevalence A-769662 cell line of RA is about 1% in the industrialized world and the major genetic contribution involves HLA class II alleles dominated by HLA DR*0101, DR*0401, and DR*0404 molecules in Caucasian

populations 1. These alleles share a highly homologous amino acid sequence at positions 67–74 of the third hypervariable region of the DRβ chain, termed the shared epitope 2, affecting peptide binding and T-cell recognition. Synovial tissue of inflamed joints is characterized by massive infiltration of T cells mostly of the Th1 subset, B cells, macrophages, and mast cells 3. Based on the abundance of T cells and the association of RA susceptibility with certain MHC class II Bupivacaine genotypes, it has been hypothesized that disease-associated

HLA-DR alleles present arthritogenic peptides leading to the stimulation and expansion of autoantigen-specific T cells in the joints and/or draining lymph nodes. Humoral and/or cellular immune responses against multiple autoantigens have been detected in arthritic patients or murine arthritis models. These include joint-specific proteins such as collagen, cartilage proteoglycan, cartilage oligomeric matrix protein, cartilage gp39, as well as ubiquitously expressed proteins such as heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2), keratin/filaggrin, fibrinogen, the stress protein BiP, and glucose 6-phosphate isomerase 4. These antigens have been studied mostly at the level of Ab production. Thus, some autoantibodies such as rheumatoid factor and Ab against deiminated (citrullinated) antigens have considerable diagnostic significance in RA 4. Although some of these autoantigens have been shown to induce T-cell reactivity 4, 5, information regarding autoantigen-specific T-cell responses in patients is limited and even contradictory 6. Moreover, the identification of autoantigenic T-cell epitopes has remained scarce and the role of T-cell responses in RA pathogenicity is still unresolved 5.