ALTERATIONS IN THE O-LINKED GLYCOSYLATION OF IgA1 IN CHILDREN WITH HENOCH-SCHONLEIN PURPURA. • 1848

Abstract

IgA plays a central role in the immunopathogenesis of Henoch-Schonlein purpura (HSP). Although there are two subclasses of IgA, HSP is associated with abnormalities involving only IgA1, but not IgA2. The reasons for the exclusive involvement of IgA1 in the pathogenesis of HSP remain unclear. One important difference between IgA1 and IgA2 is that IgA1 contains a heavily glycosylated hinge region between the CH1 and CH2 domains of the heavy chain. The hinge region oligosaccharides of IgA1 consist of galactose (Gal) plus N-acetylgalactosamine (GalNAc) which is O-linked to serine or threonine. Approximately 75% of the Gal residues are sialylated. Thus, the typical glycosylation pattern is Serine - GalNAc - Gal - Sialic acid. IgA2 contains no heavy chain hinge region, and therefore no O-linked glycosylation sites. The present study was performed to examine the O-linked glycosylation of IgA1 in 28 children with HSP and 26 control children. Plant lectins with the following binding specifities were used: Table The binding of each lectin to serum IgA1 was measured by enzyme immunoassay. There was no difference in the binding of Jacalin to IgA1 from HSP patients compared to controls (P = 0.5). The binding of Peanut lectin to IgA1 was significantly greater in HSP patients compared to controls (P = 0.007). Since sialic acid inhibits the binding of Peanut lectin to GalNAc - Gal, these results suggest there was less sialic acid in the O-linked oligosaccharides of IgA1 from patients with HSP compared to controls. Indeed, the binding of the sialic acid specific Elderberry lectin to IgA1 was significantly lower in HSP patients compared to controls (P = 0.004). The results of this study indicate that the O-linked oligosaccharides of IgA1 from patients with HSP are deficient in sialic acid. This alteration in the glycosylation of IgA1 may explain the exclusive involvement of IgA1 in HSP, and account for many of the immunologic and histologic features of the syndrome.