Immunostaining of galactose-deficient IgA1 by KM55 is not specific for immunoglobulin A nephropathy

Immunoglobulin A nephropathy (IgAN nephropathy, IgAN) is named for the renal pathological features of IgA-dominant immunoglobulin deposition. IgA deposits, however, may also occur in other diseases, from liver disease and inflammation to chronic infections and tumors. Now increasing studies have suggested that galactose-deficient IgA1 (Gd-IgA1) plays a critical role in the pathogenesis of IgAN. This study aims to investigate whether the Gd-IgA1-specific antibody KM55 contributes to differentiating primary IgAN from other diseases with IgA deposits. In this retrospective study, we enrolled 100 Chinese patients with IgA deposits in renal biopsies, including IgAN(n = 40), IgAN with hepatitis B virus antigen deposits(n = 14), IgA vasculitis(n = 16), lupus nephritis(n = 11), incidental IgA deposits(n = 13) and negative controls(n = 6). Double immunostaining of Gd-IgA1 and IgA was performed in all biopsies. There were similar patterns of Gd-IgA1 deposition in primary IgAN, IgA vasculitis, and IgAN with hepatitis B virus antigen deposits. Gd-IgA1 staining could also be seen in patients with lupus nephritis and incidental IgA deposits, but the intensity was significantly lower than IgAN, and the optimal cutoff was 2+ staining for differential diagnosis. Every increase in KM55 staining intensity of 1+ was associated with an increase in the odds of primary IgAN (OR: 4.399; 95% CI: 1.725–11.216). Immunostaining for Gd-IgA1 by KM55 is not specific for IgA nephropathy, but weak or negative staining may favor incidental IgA deposits.