Underglycosylation of IgA1 Hinge Plays a Certain Role for Its Glomerular Deposition in IgA Nephropathy

作者：Yoshiyuki Hiki, Tohru Kokubo, Hitoo Iwase, Y Masaki, Takashi Sano, Atsushi Tanaka, Kazunori Toma, Kyoko Hotta, Yutaka Kobayashi · 发表于：Journal of the American Society of Nephrology · 年份：1999 · DOI：10.1681/asn.v104760 · 被引用次数：120 · 研究领域：Renal Diseases and Glomerulopathies、Monoclonal and Polyclonal Antibodies Research、Glycosylation and Glycoproteins Research

This study was performed to isolate and investigate the IgA1 that could accumulate in glomeruli (glomerulophilic IgA1). IgA1 was fractionated by the electric charge and the reactivity to Jacalin. Serum IgA1 of IgA nephropathy patients was separated and fractionated using a Jacalin column and subsequent ion-exchange chromatography. The fractions were divided into three groups of relatively cationic (C), neutral (N), and anionic (A). IgA1 was also divided into Jacalin low (L), intermediate (I), and high (H) affinity fractions by serial elution using 25, 100, and 800 mM galactose. The left kidneys of Wistar rats were perfused with 2, 5, or 10 mg of each group of IgA1. The rats were sacrificed 15 min, 30 min, 3 h, or 24 h after the perfusion. The accumulation of each IgA1 in the glomeruli was then observed by immunofluorescence. The IgA1 of the fractions N and H separated by the two methods was definitely accumulated in the rat glomeruli with a similar pattern. The electrophoresis revealed that the macromolecular IgA1 was increased in fraction H compared with other fractions. Therefore, Jacalin high-affinity IgA1(fraction H) was applied on a diethylaminoethyl column and divided into electrically cationic (HC), neutral (HN), and anionic (HA). Only the asialo-Galbeta1,3GalNAc chain was identified in the fraction HN IgA1 by gas-phase hydrazinolysis. Furthermore, the IgA1 fraction was strongly recognized by peanut agglutinin, Vicia Villosa lectins, and antisynthetic hinge peptide ant...