劉肖帥, 葛魯娜, 韓金祥, 常曉天, 朱有名, 王世立
山東省醫(yī)學* *生物技術(shù)藥物重點實驗室 山東省罕少見病重點實驗室 山東省醫(yī)藥生物技術(shù)研究中心 濟南 250062

Key Words： 類風濕關(guān)節(jié)炎 肽基*脫亞胺酶4 SNP 瓜氨酸化 抗PADI4抗體

Abstract

類風濕關(guān)節(jié)炎（RA）是一種病因和發(fā)病機制尚不清楚的自身免疫疾病,一般認為是由多種遺傳因素和環(huán)境因素共同作用的結(jié)果。遺傳因素中以組織相容性白細胞抗原HLAzui為重要,另外作為非HLA的肽基*脫亞胺酶4（PADI4）也參與了RA的發(fā)病。PADI4是一種翻譯后修飾酶,可在鈣離子存在的情況下將*殘基轉(zhuǎn)化為瓜氨酸殘基,瓜氨酸化后的蛋白質(zhì)往往改變其分子構(gòu)象,從而導致其生化活性亦發(fā)生改變。在不用種族的人群中,PADI4基因多態(tài)性與RA的易感性不盡相同。PADI4在RA患者血清中含量明顯升高,在機體內(nèi)產(chǎn)生自身抗PADI4抗體,并且PADI4瓜氨酸化多種蛋白質(zhì)引起機體自身的免疫反應(yīng)參與RA的發(fā)生與發(fā)展。近些年來的其他研究表明PAID4也參與了腫瘤、潰瘍性結(jié)腸炎、多發(fā)性硬化癥的發(fā)病。盡管針對PADI4的研究已經(jīng)取得了很多重大進展,但是仍然存在很多懸而未決的問題等待科研工作者進一步的研究和證實。

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.