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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: Immunostaining for Gd-IgA1 by KM55 is not specific for IgA nephropathy, but weak or negative staining may favor incidental IgA deposits.

Keywords: Galactose-deficient IgA1; Hepatitis B virus; IgA; IgA nephropathy; IgA vasculitis; Renal biopsy.