ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2025
Perlecan is a novel target of autoantibodies in anti-glomerular basement membrane disease.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- The Mechanism and Application of Traditional Chinese Medicine Nano-Formulations in the Treatment of Renal Fibrosis.International journal of nanomedicine · 2026Review
- Elevated serum soluble α3(IV)NC1 correlates with kidney injury and worse outcome in patients with anti-glomerular basement membrane disease.Frontiers in immunology · 2026Article
- The multiple autoantibodies in anti-GBM disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
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Abstract
backgroundAnti-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.
methodsA 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.
resultsCirculating 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 perlecan. This subgroup had the highest prevalence of lung haemorrhage [66.7% (10/15)] and incidence of end-stage kidney disease events [93.3% (14/15)], indicating a more aggressive immune-mediated tissue injury among these patients.
conclusionPerlecan expands the repertoire of target antigens in anti-GBM disease. The discovery of autoantibodies against perlecan identified a 'triple-positive' subgroup with a more severe clinical phenotype among patients with anti-GBM disease. The pathogenic role of autoimmunity against perlecan and the pathophysiology of the co-existence of three autoantibodies merit further investigation in the future.
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