TP53 mutations coincide with the ectopic expression of activation-induced cytidine deaminase in the fibroblast-like synoviocytes derived from a fraction of patients with rheumatoid arthritis.

摘要: Main features of rheumatoid arthritis (RA), hyperplasia fibroblast-like synoviocytes (FLS) and joint destruction are caused by inflammatory cytokines produced in chronic autoimmune inflammation. Cell-intrinsic acquisition tumour-like phenotypes RA-FLS could also be responsible for the aggressive proliferation invasion, which supported fact that some cases has mutations a tumour suppressor gene TP53. However, underlying molecular mechanism TP53 not yet been clarified. Recently it reported non-lymphoid cells tissues express ectopically activation-induced cytidine deaminase (AID) induces somatic hypermutations, only at immunoglobulin (Ig) variable regions germinal centre B lymphocytes but coding Real-time polymerase chain reaction (PCR) analyses revealed more than half (five nine) lines we established showed markedly increased expression AID. AID transcription was augmented necrosis factor (TNF)-alpha even physiological concentration beta-oestradiol induce osteoarthritis-FLS. Furthermore, AID-positive presented higher frequency Cytological immunohistochemical demonstrated clearly ectopic FLS RA synovium. These data suggested strongly novel consequence RA; causes dysfunction TP53, leading to properties RA-FLS.