Recurrent Goodpasture's disease secondary to a monoclonal IgA1-κ antibody autoreactive with the α1/α2 chains of type IV collagen

Dorin Bogdan Borza, Marcio F. Chedid, Selene Colon, Donna J. Lager, Nelson Leung, Fernando Custodio Fervenza

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Goodpasture's disease is characterized by crescentic glomerulonephritis and lung hemorrhage in the presence of anti-glomerular basement membrane (anti-GBM) antibodies. This disease usually is mediated by IgG autoantibodies directed against the noncollagenous domain of the α3(IV) collagen chain, the Goodpasture autoantigen. In rare cases, anti-GBM antibodies of IgA or IgM class are involved, but their specificity has not been determined, and their target antigen remains unknown. The authors present the case of a 62-year-old man with anti-GBM disease mediated by a monoclonal IgA-κ antibody, which progressed to end-stage renal disease despite intensive immunosuppression. The patient underwent living-related kidney transplantation, but lung hemorrhage and crescentic glomerulonephritis recurred, causing the loss of the allograft 2 years later. Indirect immunofluorescence found the presence of circulating IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoabsorbent assay and Western blot as the α1/ α2(IV) collagen chains. Sensitivity to digestion with collagenase indicated that IgA bound to epitopes located in the collagenous domain. This is the first case of recurrent Goodpasture's disease secondary to an autoreactive IgA antibody. The specificity of an IgA antibody implicated in the pathogenesis of anti-GBM disease has been investigated for the first time, identifying the α1/α2(IV) collagen chains as a novel target for nephritogenic antibodies.

Original languageEnglish (US)
Pages (from-to)397-406
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume45
Issue number2
DOIs
StatePublished - Feb 2005

Fingerprint

Collagen Type IV
Immunoglobulin A
Monoclonal Antibodies
Antibodies
Anti-Glomerular Basement Membrane Disease
Glomerular Basement Membrane
Collagen
Glomerulonephritis
Hemorrhage
Lung
Antibody Specificity
Autoantigens
Collagenases
Indirect Fluorescent Antibody Technique
Basement Membrane
Autoantibodies
Kidney Transplantation
Immunosuppression
Chronic Kidney Failure
Allografts

Keywords

  • α1/α2 chains of type IV collagen
  • Anti-glomerular basement membrane (GBM) disease
  • Crescentic glomerulonephritis
  • Goodpasture's disease
  • IgA-κ antibodies
  • Kidney transplantation
  • Paraproteinemia
  • Pulmonary hemorrhage

ASJC Scopus subject areas

  • Nephrology

Cite this

Recurrent Goodpasture's disease secondary to a monoclonal IgA1-κ antibody autoreactive with the α1/α2 chains of type IV collagen. / Borza, Dorin Bogdan; Chedid, Marcio F.; Colon, Selene; Lager, Donna J.; Leung, Nelson; Fervenza, Fernando Custodio.

In: American Journal of Kidney Diseases, Vol. 45, No. 2, 02.2005, p. 397-406.

Research output: Contribution to journalArticle

Borza, Dorin Bogdan ; Chedid, Marcio F. ; Colon, Selene ; Lager, Donna J. ; Leung, Nelson ; Fervenza, Fernando Custodio. / Recurrent Goodpasture's disease secondary to a monoclonal IgA1-κ antibody autoreactive with the α1/α2 chains of type IV collagen. In: American Journal of Kidney Diseases. 2005 ; Vol. 45, No. 2. pp. 397-406.
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