Is sialylation of IgA the agent provocateur of IgA nephropathy?

Abstract

In IgA nephropathy (IgAN), the mechanisms responsible for deposition of IgA1 in the glomerular mesangium, and subsequent initiation of glomerular injury in some patients, remain unclear. Much research evidence now demonstrates that the O-glycosylation of IgA1 is abnormal in IgAN, and that this is potentially pathogenic. However, the exact nature of the O-glycoyslation abnormality, and the metabolic processes resulting in its production, are not well understood. Progress in this field has partly been limited by the lack of a suitable animal model, because the IgA of laboratory animals is not O-glycosylated. In this paper, Suzuki and colleagues have established B cell lines from patients with IgAN that produce IgA1 with abnormal O-glycosylation. This has allowed them to show that abnormal IgA1 carries an increased proportion of O-glycans terminating in sialic acid rather than the normal galactose units (Figure 1), and that this is associated with increased mRNA expression and activity of the sialylating enzyme ST6GalNAcII, and decreased expression and activity of the galactosylating enzyme C1GalT1. These findings contribute new insights to the study of defective IgA1 O-galactosylation and mark a significant step forward in the field of IgAN research