Identification of diagnostic markers for lupus nephritis

狼疮性肾炎诊断标志物的鉴定

基本信息

批准号：
8606402
负责人：
Kenneth R MCLEISH
金额：
$ 18.67万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-18 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8606402
关键词：
Actinin Address Adrenal Cortex Hormones African American Antibodies Antigen Targeting Antigen-Antibody Complex Antineutrophil Cytoplasmic Antibodies Autoantibodies Binding Biological Markers Biopsy Cerebritis Classification Collaborations Collagen Type IV Deposition Development Diagnostic Disease Early Diagnosis Epitopes Functional disorder Glomerular Capillary Heparitin Sulfate Hepatitis C Idiopathic Membranous Nephropathy Immunosuppressive Agents Kidney Kidney Diseases Kidney Failure Laminin Lupus Lupus Nephritis Membranoproliferative Glomerulonephritis Membranous Glomerulonephritis Modeling Morbidity - disease rate Mus Neurons Nuclear Nucleosomes Outcome Pathogenesis Patients Phospholipase A2 Plant Antigens Plants Prevalence Proteins Proteomics Recombinant Proteins Reporting Serum Systemic Lupus Erythematosus Tissues base cross reactivity mortality mouse model novel therapeutics podocyte public health relevance receptor therapy development

项目摘要

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.

描述（由申请人提供）：肾脏参与全身性红斑狼疮（SLE），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。这些患者中有15％至40％的肾脏活检描述了膜狼疮肾炎（MLN）（V类）。 LN所有类别的发病机理是含有自身抗体的免疫复合物的肾小球沉积。已经提出了三个假设，描述了如何沉积在肾小球中的含有肾磷酸抗体的免疫复合物，即循环免疫复合物的沉积，抗核抗体与肾小球中“种植”的抗体的结合，以及抗核酸抗体反应性，抗核抗体抗体反应性与玻璃纤维组成的抗体反应性。一种与本应用中提出的类似的蛋白质组学方法用于确定M型磷脂酶A2受体（PLA2R）的自身抗体负责在特发性膜性膜肾病中免疫复合物沉积。该抗体存在于70％至80％的特发性膜性肾病患者中，但在MLN患者中不存在。这表明有一个新的假设，即MLN患者针对肾小球毛细管的内源成分产生独特的自身抗体。当前的建议将使用我们组成功采用的蛋白质组学方法在特发性膜肾病中识别并验证引起MLN自身抗体的特定特定肾小球蛋白。