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. 2002 Jan 8;16(1):11–19. doi: 10.1002/jcla.2035

Increased sialylation of polymeric λ‐IgA1 in patients with IgA nephropathy

Joseph CK Leung 1, Sydney CW Tang 1, Daniel TM Chan 1, Sing Leung Lui 1, Kar Neng Lai 1,✉
PMCID: PMC6807889  PMID: 11835525

Abstract

The mechanism of mesangial IgA deposition is poorly understood in IgA nephropathy (IgAN). Abnormal glycosylation of carbohydrate moieties in the hinge region of the IgA molecule has recently attracted much attention. In this report, we studied galactosylation and sialylation profiles in κ‐ and λ‐IgA1 from patients with IgAN. Total serum IgA1 was isolated from patients with IgAN or healthy controls by jacalin‐affinity chromatography. Six fractions of molecular weight (MW) 50–1,000 kDa were separated by fast protein liquid chromatography (FPLC). Four lectin‐binding assays were used to study the sialylation and the presence of terminal galactose or N‐acetylgalactosamine (GalNAc) in the O‐linked carbohydrate moieties of κ‐ or λ‐IgA1. Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA) lectin recognize α(2,3)‐ and α(2,6)‐linked sialic acid, respectively. Peanut agglutinin (PNA) and Helix aspersa (HA) lectin recognize terminal galactose and GalNAc, respectively. Reduced HA was demonstrated in macromolecular κ or λ‐IgA1 (300–825 kDa) isolated from patients with IgAN (P < 0.05 compared with healthy controls). Lambda‐ but not κ‐IgA1 from patients with IgAN bound less to PNA (P < 0.05). The α(2,3)‐linked sialic acid content in λ‐ but not κ‐IgA1 of MW 150–610 kDa from patients was higher than that of controls (P < 0.005). The α(2,6)‐linked sialic acid content in λ‐IgA1 (300–825 kDa) and κ‐IgA1 (150–610 kDa) from patients was also higher than that of controls. This unusual glycosylation and sialylation pattern of the λ‐IgA1 may have important implications for the pathogenesis of IgAN, as both the masking effect of sialic acid on galactose and the reduced galactosylation will hinder the clearance of macromolecular λ‐IgA1 by asialoglycoprotein receptor of hepatocytes. The negative charge from sialic acid may also favor mesangial deposition of macromolecular λ‐IgA1 in IgAN. J. Clin. Lab. Anal. 16:11–19, 2002. © 2002 Wiley‐Liss, Inc.

Keywords: IgA nephropathy, glycosylation, sialylation, IgA1, polymeric IgA, λ‐IgA

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