Rizk DV, Saha MK, Hall S, et al. - In view of the consideration that IgA nephropathy (IgAN) is caused by glomerular deposition of circulating immune complexes of IgG bound to galactose-deficient IgA1 (Gd-IgA1), researchers here focussed on the failure of routine immunofluorescence microscopy in detection of IgG in many kidney biopsies from patients with IgAN and tested the specificity of IgG in immunodeposits. Remnant frozen kidney-biopsy specimens from 34 patients with IgAN were used; 14 were IgG-positive and 20 were IgG-negative by routine immunofluorescence microscopy. Controls comprised of six patients with primary membranous nephropathy and eight with lupus nephritis. Remnant IgAN kidney-biopsy specimens yielded IgG specific for Gd-IgA1, even when routine immunofluorescence did not detect IgG. Using confocal microscopy, they confirmed colocalization of glomerular IgA and IgG in biopsies, including those negative for IgG by routine immunofluorescence microscopy. This suggests the two form a complex. Results thereby revealed the pivotal role of IgG autoantibodies in IgAN, and support the hypothesis that Gd-IgA1–specific IgG autoantibodies are involved in the pathogenesis of the disease.