刘肖帅, 葛鲁娜, 韩金祥, 常晓天, 朱有名, 王世立
山东省医学* *生物技术药物重点实验室 山东省罕少见病重点实验室 山东省医药生物技术研究中心 济南 250062

Key Words： 类风湿关节炎 肽基*脱亚胺酶4 SNP 瓜氨酸化 抗PADI4抗体

Abstract

类风湿关节炎（RA）是一种病因和发病机制尚不清楚的自身免疫疾病,一般认为是由多种遗传因素和环境因素共同作用的结果。遗传因素中以组织相容性白细胞抗原HLAzui为重要,另外作为非HLA的肽基*脱亚胺酶4（PADI4）也参与了RA的发病。PADI4是一种翻译后修饰酶,可在钙离子存在的情况下将*残基转化为瓜氨酸残基,瓜氨酸化后的蛋白质往往改变其分子构象,从而导致其生化活性亦发生改变。在不用种族的人群中,PADI4基因多态性与RA的易感性不尽相同。PADI4在RA患者血清中含量明显升高,在机体内产生自身抗PADI4抗体,并且PADI4瓜氨酸化多种蛋白质引起机体自身的免疫反应参与RA的发生与发展。近些年来的其他研究表明PAID4也参与了肿瘤、溃疡性结肠炎、多发性硬化症的发病。尽管针对PADI4的研究已经取得了很多重大进展,但是仍然存在很多悬而未决的问题等待科研工作者进一步的研究和证实。

Abstract

Rheumatoid arthrisits（RA） is a systemic autoimmune disease that exact pathogeny is unknown. Generally speaking, the pathogenic factors of RA are due to environmental factors and genetic factors. In genetic factors histocompatibility leukocyte antigen（HLA） is one of the most important elements. In addition, peptidylarginine deiminase 4 （PADI4） which does not belong to HLA has been thought to participate in the development of RA recently. PADI4 can catalyse peptidylarginine to citrulline in the presence of Ca2+. This action leads to posttranslational modification of protein. Citrullination brings to conformation change in peptide chains and active sites transformation. In various population, the relation between the SNP which located in PADI4 gene and pothogenesy of RA is different. PADI4 is up-regulated in RA patient’s blood serum and results in autoimmune antibody. PADI4 also citrullinates various protein induced autoimmune response which contributes to the development of RA. Lay other reports show that PADI4 is also relative to tumors, ulcerative colitis as well as multiple sclerosis. Although researches about PADI4 have been made a lot of significant progresses, abundant of unknow have always been existing.