Underglycosylation of IgA1 hinge plays a certain role for its glomerular deposition in IgA nephropathy.

Abstract

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 antibody. These results indicated that the IgA1 molecules having the underglycosylated hinge glycopeptide played a certain role in the glomerular accumulation of IgA1 in IgA nephropathy.

• Authors: Y Hiki, T Kokubo, H Iwase, Y Masaki, T Sano, A Tanaka, K Toma, K Hotta, Y Kobayashi
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 10 Issue 4 Pg. 760-9 (Apr 1999) ISSN: 1046-6673 [Print] United States
• PMID: 10203360 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin A
• Immunoglobulin Fragments
• Interferon Inducers
• Lectins
• Peptide Fragments
• Plant Lectins
• Polysaccharides
• jacalin

Topics

• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Electrophoresis, Polyacrylamide Gel
• Enzyme-Linked Immunosorbent Assay
• Female
• Glomerulonephritis, IGA (immunology, pathology)
• Glycosylation
• Humans
• Immunoglobulin A (chemistry, metabolism)
• Immunoglobulin Fragments (chemistry, metabolism)
• Interferon Inducers (pharmacology)
• Kidney Glomerulus (drug effects, immunology, pathology)
• Lectins (metabolism, pharmacology)
• Peptide Fragments (chemistry, metabolism)
• Plant Lectins
• Polysaccharides (analysis)
• Rats
• Rats, Wistar
• Reference Values