抗C3b抗体在狼疮性肾炎发病机制中的研究

狼疮性肾炎发病机制目前未完全阐明，补体缺陷与凋亡物质清除障碍在其中起重要作用。申请者前期研究发现补体旁路异常活化是本病发病机制中的重要环节。鉴于C3b是补体旁路活化的中心环节，也是免疫复合物清除的关键因子，我们推测抗C3b抗体引起的C3b功能异常可能参与了本病的发病。我们的前期研究发现抗C3b抗体阳性的狼疮性肾炎患者血清C3水平更低、抗ds-DNA抗体滴度更高，提示抗C3b抗体可能参与了致病，但其确切机制仍不明确。本研究拟通过体外及动物实验，探讨抗C3b抗体对C3b功能的影响，以阐明抗C3b抗体在狼疮性肾炎补体活化及清除凋亡过程中的致病作用，为临床防治该病提供新的理论和实验依据。

The pathogenesis of lupus nephritis (LN) has not been fully understood. The complement deficiency and persistence of apoptotic cells had been demonstrated to play important roles in the process of LN. In our preliminary study, we found that the complement alternative pathway activation might be crucial for the disease development. Since C3b is one of the key proteins in alternative pathway activation and clearance of immunocomplex, we speculate that anti-C3b antibodies may be involved in the pathogenesis of lupus nephritis through suppression of C3b functions. We had found that patients with anti-C3b antibodies had lower serum C3 levels and higher anti-ds-DNA antibody titers, which suggested the pathogenic effect of anti-C3b antibody. However, the actual roles of anti-C3b antibody were still unknown. In this study, we aimed to elucidate whether the anti-C3b antibody was involved in the pathogenesis of lupus nephritis through affecting the functions of C3b, disturbing the complement activation and apoptosis clearance both in vivo and in vitro, and we also intended to observe the associations between anti-C3b antibody and renal injury parameters in MRL/lpr mice models. This study would illuminate one of the etiologies of lupus nephritis and be meaningful in providing new directions for the diagnosis and treatment of this disease.