RA患者血液及关节滑膜液（SF）中存在大量免疫复合物（IC）及抗瓜氨酸化蛋白抗体（ACPA），IC通过激活补体、活化吞噬细胞并释放细胞因子（CK）等炎性介质，引起滑膜炎性损伤。本课题拟在前期研究血清ACPA特异性IC（ACPA-IC）刺激成纤维样滑膜细胞（FLS）增殖及CK释放的基础上，研究ACPA-IC在RA滑膜组织中的表达；从RA SF中提取ACPA-IC（sfACPA-IC），MALDI-TOF-MS等法鉴定sfACPA-IC中瓜氨酸化抗原成分；体外培养FLS，研究sfACPA-IC对FLS增殖的影响；液态芯片法分析sfACPA-IC对FLS分泌CK和基质金属蛋白酶(MMP)的影响；研究sfACPA-IC介导FLS增殖及炎性因子分泌的信号通路分子的变化。上述研究可望进一步阐述sfACPA-IC在RA滑膜炎性损伤中的作用及其机制，为探讨RA新的诊断和治疗分子靶标提供理论和实验依据。

The presence of immune complexes (IC) and anti-citrullinated protein antibodies (ACPA) are abundant in serum and synovial fluid (SF) of RA patients, which is likely to contribute to the pathogenesis of RA and to articular damage. Since they are able to activate the complement, stimulate phagocytes through their Fc receptor and release cytokines (CKs), metalloproteinases (MMPs) and reactive oxygen intermediates. Based on the previous study findings that ACPA-IC from RA sera could stimulate the proliferation of fibroblast-like synoviocytes (FLS) and promote the release of inflammatory cytokines, we would continue to investigate the expression of ACPA-IC on synovial tissues from patients with RA by immunohistochemistry; extract the ACPA-IC from synovial fluid (sfACPA-IC) using affinity chromatography and identify the antigens of sfACPA-IC utilized Western blot or ELISA; screen and identify the citrullinated antigens in sfACPA-IC applied the MALDI-TOF-MS; study the effects of FLS proliferation and CKs and MMPs secretions stimulated by FLS cultured in vitro; analyze the activation of signaling pathway components (NF-κB, p38, JNK, ERK. etc) which mediated the FLS proliferation and inflammatory cytokines secretion. The above work would further explore the mechanism and roles of sfACPA-IC in RA synovitis, and we hope to provide breakthrough diagnostic indicators and therapeutic targets for RA.