Ohmura Koichiro
Department of rheumatology and clinical immunology, Graduate school of medicine, Kyoto University.
Nihon Rinsho Meneki Gakkai Kaishi. 2009 Dec;32(6):484-91. doi: 10.2177/jsci.32.484.
These days, rheumatoid arthritis (RA) is reported to be subclassified into two subsets by anti-citrullinated peptide antibody (ACPA) positivity. Clinically, ACPA positive RA tends to develop more severe arthritis than ACPA negative RA. In addition, a lot of reported susceptibility genes to RA (ie. HLA-DRB1()04, PTPN22, TRAF1/C5, CTLA4) are found to be associated only with ACPA positive RA but not with ACPA negative RA. It is getting clear that HLA-DRB1()04, which was believed to be primarily associated with RA, is not a primary risk factor but ACPA is. Then, a hypothesis for the disease mechanism of ACPA positive RA is set as follows; citrullination possibly due to smoking, etc, provokes ACPA production in individuals who have susceptibility alleles of genes including HLA, followed by joint inflammation in autoantibody-dependent manner. The search for susceptibility genes for ACPA negative RA is slowly progressing, but only a few genes are so far reported: HLA-DRB1()03 for Caucasian, HLA-DRB1()09 for Japanese, IRF5 and STAT4. When we investigate the disease mechanisms of RA, we should manage independently the two disease subsets : ACPA positive and ACPA negative RA.
近年来，据报道类风湿关节炎（RA）可根据抗瓜氨酸化肽抗体（ACPA）阳性分为两个亚组。临床上，ACPA阳性的RA往往比ACPA阴性的RA发展为更严重的关节炎。此外，许多已报道的RA易感基因（如HLA - DRB1（）04、PTPN22、TRAF1/C5、CTLA4）仅与ACPA阳性的RA相关，而与ACPA阴性的RA无关。越来越清楚的是，曾被认为主要与RA相关的HLA - DRB1（）04并非主要危险因素，而ACPA才是。于是，ACPA阳性RA的疾病机制假说如下：可能由于吸烟等导致的瓜氨酸化，在具有包括HLA等基因易感等位基因的个体中引发ACPA产生，随后以自身抗体依赖的方式导致关节炎症。对ACPA阴性RA易感基因的研究进展缓慢，但目前仅报道了少数几个基因：白种人的HLA - DRB1（）03、日本人的HLA - DRB1（）09、IRF5和STAT4。当我们研究RA的疾病机制时，应分别处理ACPA阳性和ACPA阴性这两个疾病亚组。
