Evaluation of IgA1 O-glycosylation in Henoch-Schönlein Purpura Nephritis Using Mass Spectrometry.

Abstract

BACKGROUND:

Glomerular deposition of IgA1 is a common feature of Henoch-Schönlein purpura nephritis (HSPN) and is indistinguishable from that seen in IgA nephropathy (IgAN). Serum IgA1 is abnormally O-glycosylated in IgA nephropathy, which may contribute to the development of glomerular injury. Abnormal O-glycosylated IgA1 was also detected in HSPN using lectin enzyme-linked immunosorbent assay; however, this method cannot provide the exact structural information of O-glycans. Mass spectrometry is an effective means of quantification of O-glycans, and there is no report to evaluate IgA1 O-glycans in HSPN using mass spectrometry.

MATERIALS AND METHODS:

We investigated O-glycosylation profile in serum IgA1 from 7 HSPN recipients, 26 IgAN recipients, 25 recipients with other kidney diseases (OKDs), and 26 normal healthy donors using mass spectrometry.

RESULTS:

Of the 14 GalNac-Gal combinations detected using mass spectrometry, the percentage of the only 6GalNAc-2Gal combination was significantly different between HSPN and IgAN. The percentage of GalNAc 3 in HSPN recipients was significantly higher than that in OKDs recipients and healthy donors (P = .0027 and P < .0001, respectively). Inversely, the percentage of GalNAc 5 in HSPN recipients was significantly lower than that in OKDs recipients and healthy donors (P = .0008, P < .0001, respectively). Moreover, the Gal content and the Gal/GalNAc ratio of HSPN recipients were significantly lower than OKDs recipients and healthy donors.

CONCLUSIONS:

Examination of Henoch-Schönlein purpura recipients revealed that the number of GalNAc fell and the Gal attachment to GalNAc was reduced compared to other kidney diseases and healthy donors. The IgA1 O-glycosylation profile of HSPN was very similar to that of IgAN.

• Authors: Shigeaki Nakazawa, Ryoichi Imamura, Masataka Kawamura, Taigo Kato, Toyofumi Abe, Hirotsugu Iwatani, Kazuaki Yamanaka, Motohide Uemura, Hidefumi Kishikawa, Kenji Nishimura, Michiko Tajiri, Yoshinao Wada, Norio Nonomura
• Journal: Transplantation proceedings (Transplant Proc) Vol. 51 Issue 5 Pg. 1481-1487 (Jun 2019) ISSN: 1873-2623 [Electronic] United States
• PMID: 31084922 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Immunoglobulin A
• Acetylgalactosamine

Topics

• Acetylgalactosamine (analysis, metabolism)
• Female
• Glomerulonephritis, IGA (metabolism, pathology)
• Glycosylation
• Humans
• IgA Vasculitis (metabolism, pathology)
• Immunoglobulin A (chemistry, metabolism)
• Male
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (methods)