TY - JOUR
T1 - Antigenic Heterogeneity of IgA Anti-GBM Disease
T2 - New Renal Targets of IgA Autoantibodies
AU - Ho, Julie
AU - Gibson, Ian W.
AU - Zacharias, James
AU - Fervenza, Fernando
AU - Colon, Selene
AU - Borza, Dorin Bogdan
N1 - Funding Information:
Support: This study was supported in part by National Institutes of Health (NIH) grant P01 DK065123 to Dorin-Bogdan Borza. The Human Tissue Acquisition and Pathology Shared Resource at Vanderbilt University is supported by NIH grant P30 CA68485.
Funding Information:
Financial Disclosure: Dr Ho is funded by a Bristol Myers Squibb Cardiovascular Research Fellowship.
PY - 2008/10
Y1 - 2008/10
N2 - Anti-glomerular basement membrane (anti-GBM) disease is an aggressive form of glomerulonephritis, usually mediated by immunoglobulin G (IgG) autoantibodies to the noncollagenous (NC1) domain of α3(IV) collagen. Less is known about the target antigen(s) in patients with atypical anti-GBM disease involving IgA autoantibodies. We report a new case of IgA anti-GBM disease in a patient with a history of proliferative lupus nephritis who presented with increasing creatinine levels, proteinuria, and hematuria, but no clinical or serological evidence of lupus recurrence. Renal biopsy showed focal and segmental necrotizing glomerulonephritis with strong linear capillary loop IgA staining by means of immunofluorescence. Serological test results were negative for IgG or IgA autoantibodies against the α3NC1 domain. By means of immunoblotting, IgA from patient serum bound to 38- to 48-kd antigens collagenase-solubilized from human GBM, but not to purified NC1 domains of GBM collagen IV. The target of patient's IgA autoantibodies thus was identified as a novel GBM antigen, distinct from the α3NC1 domain or other known targets of anti-GBM IgA autoantibodies. Clinical resolution was attained by means of conventional treatment with steroids and cyclophosphamide. The diversity of antigens recognized by anti-GBM IgA autoantibodies highlights the importance of renal biopsy for the reliable diagnosis of this rare condition because conventional serological immunoassays likely would yield false-negative results.
AB - Anti-glomerular basement membrane (anti-GBM) disease is an aggressive form of glomerulonephritis, usually mediated by immunoglobulin G (IgG) autoantibodies to the noncollagenous (NC1) domain of α3(IV) collagen. Less is known about the target antigen(s) in patients with atypical anti-GBM disease involving IgA autoantibodies. We report a new case of IgA anti-GBM disease in a patient with a history of proliferative lupus nephritis who presented with increasing creatinine levels, proteinuria, and hematuria, but no clinical or serological evidence of lupus recurrence. Renal biopsy showed focal and segmental necrotizing glomerulonephritis with strong linear capillary loop IgA staining by means of immunofluorescence. Serological test results were negative for IgG or IgA autoantibodies against the α3NC1 domain. By means of immunoblotting, IgA from patient serum bound to 38- to 48-kd antigens collagenase-solubilized from human GBM, but not to purified NC1 domains of GBM collagen IV. The target of patient's IgA autoantibodies thus was identified as a novel GBM antigen, distinct from the α3NC1 domain or other known targets of anti-GBM IgA autoantibodies. Clinical resolution was attained by means of conventional treatment with steroids and cyclophosphamide. The diversity of antigens recognized by anti-GBM IgA autoantibodies highlights the importance of renal biopsy for the reliable diagnosis of this rare condition because conventional serological immunoassays likely would yield false-negative results.
KW - Anti-glomerular basement membrane disease
KW - autoimmune glomerulonephritis
KW - immunoglobulin A (IgA) autoantibodies
KW - systemic lupus erythematosus
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U2 - 10.1053/j.ajkd.2008.03.041
DO - 10.1053/j.ajkd.2008.03.041
M3 - Article
C2 - 18752876
AN - SCOPUS:52049118533
SN - 0272-6386
VL - 52
SP - 761
EP - 765
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 4
ER -