Identification of diagnostic markers for lupus nephritis

描述（由申请人提供）：系统性红斑狼疮（SLE）的肾脏受累，称为狼疮肾炎（LN），发生在约60%的患者中，是发病率和死亡率的主要原因。膜性狼疮性肾炎（MLN） （V级）在这些患者的肾活检中占15%至40%。所有类型LN的发病机制都是肾小球内含有自身抗体的免疫复合物的沉积。关于含有肾源性抗体的免疫复合物如何在肾小球中沉积，提出了三种假说：循环免疫复合物的沉积，抗核抗体与“种植”在肾小球中的抗原结合，以及抗核抗体与肾小球成分的交叉反应。蛋白质组学方法，类似于本申请中提出的方法，用于确定m型磷脂酶A2受体（PLA2R）的自身抗体是特发性膜性肾病中免疫复合物沉积的原因。该抗体在70% - 80%的特发性膜性肾病患者中存在，但在MLN患者中不存在。这提出了一种新的假设，即MLN患者会产生针对肾小球毛细血管内源性成分的独特自身抗体。目前的建议将使用我们小组在特发性膜性肾病中成功使用的蛋白质组学方法来鉴定和验证导致MLN的自身抗体所针对的特定肾小球蛋白。

DESCRIPTION (provided by applicant): Renal involvement in systemic lupus erythematosus (SLE), termed lupus nephritis (LN), occurs in about 60% of patients and is a leading cause of morbidity and mortality. Membranous lupus nephritis (MLN) (class V) is described in 15% to 40% of renal biopsies in these patients. The proposed pathogenesis of all classes LN is the glomerular deposition of immune complexes containing auto-antibodies. Three hypotheses describing how immune complexes containing nephritigenic antibodies are deposited in glomeruli have been proposed, deposition of circulating immune complexes, binding of anti-nuclear antibodies to antigens "planted" in the glomerulus, and cross reactivity of anti-nuclear antibodies with glomerular constituents. A proteomic approach, similar to that proposed in this application, was used to determine that an auto-antibody to the M-type phospholipase A2 receptor (PLA2R) is responsible for immune complex deposition in idiopathic membranous nephropathy. This antibody is present in 70% to 80% of patients with idiopathic membranous nephropathy, but it is not present in patients with MLN. This suggests a new hypothesis that patients with MLN develop unique auto-antibodies against an endogenous component of the glomerular capillary. The current proposal will use proteomic approaches that were successfully employed by our group in idiopathic membranous nephropathy to identify and verify specific glomerular proteins to which autoantibodies that cause MLN are directed.