Perlecan is a novel target of autoantibodies in anti-glomerular basement membrane disease

作者：Huang Kuang, Beining Wang, Xiao Jia, Zhao Cui, Xiaojuan Yu, Nan Jiang, Dorin‐Bogdan Borza, Ming‐Hui Zhao · 发表于：Nephrology Dialysis Transplantation · 年份：2025 · DOI：10.1093/ndt/gfaf153 · 被引用次数：4 · 研究领域：Vasculitis and related conditions、Autoimmune Bullous Skin Diseases、Cell Adhesion Molecules Research

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune kidney disease in which autoantibodies are directed against GBM components. Type IV collagen and laminin α5β2γ1 (laminin 521) within the GBM are two major target antigens in anti-GBM disease. Perlecan is a type of heparan sulphate proteoglycans, ubiquitously expressed in basement membranes. The present study aimed to investigate whether perlecan could be recognized by anti-GBM antibodies and further analysed the properties and clinical associations of anti-perlecan antibodies. METHODS: A total of 108 patients diagnosed with anti-GBM disease between January 2000 and December 2018 were included in the study. Additionally, 100 patients with various active glomerular diseases were utilized as disease controls, along with 40 healthy controls. Immunoglobulin G (IgG) antibodies against perlecan were detected by enzyme-linked immunosorbent assay and immunoblot. RESULTS: Circulating IgG antibodies against perlecan were detected in 18.5% (20/108) of the anti-GBM patients but not in the healthy controls or other glomerular disease controls. Anti-perlecan IgG antibodies were predominantly of the IgG3 subclass. Patients with anti-perlecan autoantibodies had a higher prevalence of lung haemorrhage than those without (55.0% versus 26.1%; P = .012). A 'triple-positive' subgroup with anti-GBM disease was identified, who had circulating autoantibodies simultaneously against type IV collagen, laminin 521 and perle...