Anti-glomerular basement membrane disease: variant forms and underlying mechanisms.

Abstract

Anti-glomerular basement membrane (GBM) disease is the most severe form of autoimmune glomerulonephritis following assaults on kidney and alveolar basement membranes by pathogenic anti-GBM antibodies. Typically, anti-GBM disease is characterized by rapidly progressive glomerulonephritis and an increased risk of lung hemorrhage, with kidney biopsy revealing ominous crescent formation. Although patient survival has improved with standard of care including plasma exchange and intensive immunosuppression in the recent decade, kidney survival still remains poor due to delayed recognition and tardy initiation of standard therapy. With the increasing understanding of the disease in clinical practice, several variant forms have been recognized. We here propose to group these forms into four categories according to their immunological properties and clinical presentations: overlapping autoimmune syndromes (anti-GBM disease with combined ANCA, concurrent membranous nephropathy, or IgA nephropathy), immunological distinct forms (Alport post-transplant anti-GBM disease, seronegative anti-GBM disease), clinical phenotypic variant forms (recurrent anti-GBM disease in native kidney, anti-GBM disease in the elderly or with normal kidney function ) and medication-associated anti-GBM disease. These patients have different features in terms of clinical manifestations, pathological findings, or prognosis compared with patients with classical anti-GBM disease. In this review, we discuss these variant forms with emphasis on their phenotypes and underlying mechanisms. An enhanced understanding of pathophysiology of anti-GBM disease variant forms can pave the way for personalized therapies tailored to patients with different presentations of the disease.