Anti–glomerular basement membrane Disease
- Anti-GBM disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and/or lungs.
- Accounts for ~10%–15% of all cases of crescentic glomerulonephritis (GN).
- Slight male preponderance and bimodal age distribution, with peaks in the 3rd decade.
- Strong HLA-gene association, with ~80% of patients inheriting an HLA-DR2 haplotype.
- Triggers: respiratory tract infections, smoking and alemtuzumab (anti-CD52 mAb) therapy
- Target of the autoimmune response is the noncollagenous (NC1) domain of the a3 chain of type IV collagen a3[IV]NC1 (Goodpasture autoantigen)
- The majority of patients (80%–90%) will present with features of rapidly progressive GN. Forty percent to 60% will have concurrent lung hemorrhage.
- Direct immunofluorescence for Ig on frozen kidney tissue is the gold-standard for diagnosis of anti-GBM that typically showing a strong linear ribbon-like IgG reactivity (rarely IgA).
- Light microscopy generally shows crescents typically of uniform age.
- Standard treatment for anti-GBM disease includes plasmapheresis, to rapidly remove pathogenic autoantibody, along with cyclophosphamide and corticosteroids, to inhibit further autoantibody production and to ameliorate end-organ inflammation.
- Recurrence in the allograft, at frequencies of up to 50% in historical series.
- Alport syndrome patients undergoing renal allograft transplant are at high risk of developing anti-GBM disease.
- Variant forms of anti-GBM disease include double-positive anti-GBM and ANCA-associated GN, anti-GBM disease associated with membranous nephropathy and “Atypical” anti-GBM disease.
References
- McAdoo SP, Pusey CD. Anti-glomerular basement membrane disease. Clin J Am Soc Nephrol. 2017;12:1162-1172.
- Gulati K, McAdoo SP. Anti-glomerular basement membrane disease. Rheum Dis Clin North Am. 2018;44:651-673.
- Moulis G, Huart A, Guitard J, et al. IgA mediated anti-glomerular basement membrane disease: An uncommon mechanism of Goodpasture’s syndrome. Clin Kidney J. 2012;5:545–548.
- Pedchenko V, Bondar O, Fogo AB. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med. 2010;363:343-54.
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