TY - JOUR
T1 - Recurrent Goodpasture's disease secondary to a monoclonal IgA1-κ antibody autoreactive with the α1/α2 chains of type IV collagen
AU - Borza, Dorin Bogdan
AU - Chedid, Marcio F.
AU - Colon, Selene
AU - Lager, Donna J.
AU - Leung, Nelson
AU - Fervenza, Fernando C.
N1 - Funding Information:
Supported in part by program project grant DK65123 (to D.-B.B.) from the National Institutes of Health.
PY - 2005/2
Y1 - 2005/2
N2 - 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.
AB - 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.
KW - Anti-glomerular basement membrane (GBM) disease
KW - Crescentic glomerulonephritis
KW - Goodpasture's disease
KW - IgA-κ antibodies
KW - Kidney transplantation
KW - Paraproteinemia
KW - Pulmonary hemorrhage
KW - α1/α2 chains of type IV collagen
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U2 - 10.1053/j.ajkd.2004.09.029
DO - 10.1053/j.ajkd.2004.09.029
M3 - Article
C2 - 15685519
AN - SCOPUS:15944409208
SN - 0272-6386
VL - 45
SP - 397
EP - 406
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -