title: Circulating anti-glomerular basement membrane antibodies with predominance of subclass IgG4 and false-negative immunoassay test results in anti-glomerular basement membrane disease.
abstract: 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.
authors.affiliation: Department of Nephrology and Transplantation, Skane University Hospital, Göteborg, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ohlsson
authors.affiliation: Department of Nephrology, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Herlitz
authors.affiliation: Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Lundberg
authors.affiliation: Department of Nephrology and Transplantation, Skane University Hospital, Göteborg, Sweden.
authors.forename: Daina
authors.initials: D
authors.lastname: Selga
authors.affiliation: Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Mölne
authors.affiliation: Eurodiagnostica AB, Malmö, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Wieslander
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Department of Nephrology, County Council of Östergötland, Linköping, Sweden. Electronic address: marten.segelmark@liu.se.
authors.forename: Mårten
authors.initials: M
authors.lastname: Segelmark
mesh_terms: D000293:Adolescent; D000328:Adult; D019867:Anti-Glomerular Basement Membrane Disease / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; C051951:antiglomerular basement membrane antibody
keywords: Anti–glomerular basement membrane (anti-GBM); Goodpasture disease; immunoglobulin G4 (IgG4)