The significance of galactose-deficient immunoglobulin A1 staining in kidney diseases with IgA deposition

Background: This study investigated the significance of galactose-deficient immunoglobulin A1 staining in kidney diseases with IgA deposition.

Methods: A total of 120 patients with IgA-dominant deposition in kidney tissues were enrolled and divided into four groups: primary IgA nephropathy (PIgAN), secondary IgA nephropathy (SIgAN), monotypic IgA nephropathy (MIgAN), and IgA variant monoclonal gammopathy of renal significance (IgA-MGRS). KM55 (the antibody of galactose-deficient immunoglobulin A1), IgA subtypes, and complement pathway factors (properdin, C4d, and C1q) were detected through immunofluorescence or immunohistochemistry analysis.

Results: KM55 and IgA double staining showed colocalization within glomeruli in all cases except for IgA-MGRS, which showed negative or weak staining of KM55 but strong staining of IgA. The PIgAN group showed the highest intensity of KM55 and KM55/IgA ratio, while these values in the IgA-MGRS group were the lowest (P < 0.01). A KM55/IgA quantified ratio of 0.78 was the optimal cut-off value to distinguish PIgAN from SIgAN, whereas a cut-off value of 0.21 was optimal to distinguish between MIgAN and IgA-MGRS. The clinicopathological characteristics showed significant differences as the groups were divided by diseases with optimal cut-off values, and these differences corresponded to the pathogenesis of each disease entity.

Conclusions: PIgAN, SIgAN, and MIgAN are caused by the deposition of abnormally glycosylated IgA1 whereas IgA-MGRS is not. The KM55/IgA quantified ratio is valuable in distinguishing PIgAN from SIgAN, as well as MIgAN from IgA-MGRS.