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Circulating anti-glomerular basement membrane antibodies with predominance of subclass IgG4 and false-negative immunoassay test results in anti-glomerular basement membrane disease.

Journal article
Authors Sophie Ohlsson
Hans Herlitz
Sigrid Lundberg
Daina Selga
Johan Mölne
Jörgen Wieslander
Mårten Segelmark
Published in American Journal of Kidney Diseases
Volume 63
Issue 2
Pages 289-93
ISSN 0272-6386
Publication year 2014
Published at
Pages 289-93
Language en
Keywords Adolescent, Adult, Anti-Glomerular Basement Membrane Disease, blood, diagnosis, immunology, Autoantibodies, biosynthesis, blood, False Negative Reactions, Female, Humans, Immunoassay, methods, Immunoglobulin G, biosynthesis, blood, Young Adult
Subject categories Urology and Nephrology


Autoantibodies against a constituent of the glomerular basement membrane (GBM), the α3-chain of type IV collagen, can cause both rapidly progressive glomerulonephritis and alveolar hemorrhage, referred to as anti-GBM disease or Goodpasture disease. Anti-GBM antibodies generally are of immunoglobulin G subclass 1 (IgG1) and can in most cases readily be detected in the circulation using enzyme-linked immunosorbent assays (ELISAs). We report 4 cases in which anti-GBM ELISA yielded negative or borderline results despite life-threatening disease. All 4 patients had positive results by IgG4 anti-GBM ELISA and all had undetectable antineutrophil cytoplasmic antibody. All cases were confirmed with kidney biopsy. Two of the patients showed higher signal in anti-GBM ELISA when using a nondenaturing coating buffer. All 4 were young women with severe alveolar hemorrhage and favorable renal outcome, suggesting that patients with predominance of IgG4 autoantibodies may constitute a distinct subgroup of anti-GBM disease. We conclude that patients with idiopathic alveolar hemorrhage can have anti-GBM disease detected by only IgG subclass-specific tests or kidney biopsy.

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