Membranous nephropathy and cerebellar degeneration with anti-GAD antibodies in type 2 diabetes mellitus

Aims To study the potential pathogenic significance of the coexistence of membranous nephropathy, cerebellar degeneration and anti-glutamic acid decarboxylase (GAD) autoantibodies in patients with diabetes. Methods We performed a direct immunocytochemistry on human kidney slides, electron microscopy on human kidney biopsy, direct immunofluorescence on human kidney biopsy. Baboon and rat kidney cell lines were fractionated and subjected to western blotting with antibodies to GAD. Results In this patient we demonstrate the presence of autoantibodies to GAD, which is highly enriched in podocytes plasma membrane and tubular cells of the kidney as well as sub-endothelial IgG and complement C3 deposits in the glomerular basement membrane (GBM). Conclusions We hypothesize the existence in this patient of a common autoimmune pathogenic mechanism with GAD as the autoantigenic determinant, underlying cerebellar degeneration and membranous nephropathy.