抗RCP抗体通过影响巨噬细胞吞噬功能参与系统性红斑狼疮发病的机制研究

系统性红斑狼疮（SLE）是一种以自身抗体增多并参与疾病发生与发展的自身免疫性疾病。我们前期通过高通量蛋白芯片筛选和酶联免疫吸附法验证，发现抗Rab偶联蛋白（RCP）抗体在SLE患者中异常高表达。基于RCP蛋白可影响巨噬细胞吞噬功能的认识，抗RCP抗体升高是否影响巨噬细胞对凋亡细胞的吞噬清除，并改变靶器官的免疫微环境，从而参与SLE发病？因此，本课题计划从以下三方面研究：1）临床相关性：SLE患者中抗RCP抗体与疾病活动度相关性，评估其作为生物标志物及诊断价值。2）体外实验：抗RCP抗体使巨噬细胞吞噬功能下降；影响吞噬相关炎症因子及信号通路。3）体内实验：正常小鼠、狼疮小鼠及巨噬细胞RCP条件敲除小鼠注射抗RCP抗体，狼疮表型观察及对靶器官巨噬细胞吞噬功能影响。本研究有助于深入了解SLE发病机制，为临床诊治提供新思路。

Systemic lupus erythematosus(SLE) is an autoimmune diseases characterized by elevation of antibodies participating in the occurrence and progress of the disease. In our pilot studies, using high-throughput protein chip screening and enzyme-linked immunosorbent assay, we detected highly increased levels of anti-Rab conjugated protein (RCP) antibodies in SLE patients. As RCP is associated with the phagocytic process of macrophages, we hypothesize that increased anti-RCP antibodies impair the phagocytic function of macrophages, then change the micro-environment of organs and contribute to the development of SLE. In this project, we will conduct the following experiments: 1) Clinical investigation: to examine the correlation between anti-RCP antibody and disease activity in SLE patients and validate anti-RCP antibody as a biomarker. 2) In vitro studies: to determine the effect of anti-RCP antibody on phagocytic process and its related cytokines and signal pathways. 3) In vivo studies: to evaluate the influence of anti-RCP antibody administration on phagocytic function and disease progression of in C57BL/6, MRL/lpr lupus mice and RCP conditional knockout in macrophages(RCP-cKO). The expected findings will provide new insights in understanding the pathogenesis and new view on the diagnose and treatment of SLE .