Review Article | Published:

Advances in human antiglomerular basement membrane disease

Nature Reviews Nephrology volume 7, pages 697705 (2011) | Download Citation

Abstract

Antiglomerular basement membrane (anti-GBM) disease is an autoimmune disorder that mostly presents as raised titers of antibodies against the GBM, rapidly progressive glomerulonephritis and pulmonary hemorrhage. The disease is caused by antibodies against noncollagenous domain of α3 chain of type IV collagen, which contains the epitopes EA and EB. The humoral and cellular immunity contributing to the initiation of anti-GBM disease has been extensively studied as a model for autoimmune diseases, although most of the data come from animal studies. The disease is rare, but diagnoses have been made in hundreds of patients. Substantial advances have been made in the understanding of human anti-GBM disease, and it can be treated successfully. In this Review we summarize the current knowledge on the prevalence, clinical manifestations, treatment and outcomes of human anti-GBM disease. We discuss findings on pathogenesis from human studies, with close attention to disease initiation and the immunological features of progression from quiescent autoimmune homeostasis in healthy individuals to fulminant anti-GBM disease. Further studies on autoreactive T cells are expected to clarify specific features of human anti-GBM disease and could lead to the development of new therapies.

Key points

  • Human anti-glomerular basement membrane (anti-GBM) disease affects all races, has an annual incidence of up to 0.5–1.0 cases per million of the general population, and is strongly linked to HLA DRB1*1501

  • Although anti-GBM glomerulonephritis is rapidly progressive in most patients, cases with persistent normal renal function with mild glomerular lesions on renal biopsy have been described

  • Double positivity for autoantibodies against the GBM and antineutrophil cytoplasmic antibodies has a much worse renal prognosis than vasculitis associated with antineutrophil cytoplasmic antibodies but a similar prognosis to that seen with antibodies against the GBM alone

  • Central tolerance towards α3(IV)NC1 is incomplete and T cells and B cells specific for the autoepitopes are not deleted and/or rendered anergic

  • Changes in the immunological features of antibodies against GBM characterize progression from quiescent autoimmune homeostasis in healthy individuals to fulminant anti-GBM disease

  • Early treatment of plasmapheresis together with immunosuppression is crucial to achieve optimum overall and renal outcomes in patients with anti-GBM disease

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Acknowledgements

The authors' work is supported by a grant from Natural Science Fund of China to the Innovation Research Group (81021004).

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  1. Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China

    • Zhao Cui
    •  & Ming-Hui Zhao

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Both authors contributed equally to researching data, discussing content, writing, and reviewing/editing this article before submission.

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Correspondence to Ming-Hui Zhao.

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https://doi.org/10.1038/nrneph.2011.89

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