Racial heterogeneity of IgA1 hinge-region O-glycoforms in patients with IgA nephropathy

Yukako Ohyama, Hisateru Yamaguchi, Soshiro Ogata, Samantha Chiurlia, Sharon N. Cox, Nikoletta Maria Kouri, Maria J. Stangou, Kazuki Nakajima, Hiroki Hayashi, Daijo Inaguma, Midori Hasegawa, Yukio Yuzawa, Naotake Tsuboi, Matthew B. Renfrow, Jan Novak, Aikaterini A. Papagianni, Francesco P. Schena, Kazuo Takahashi

Research output: Contribution to journalArticlepeer-review

Abstract

Galactose (Gal)-deficient IgA1 (Gd-IgA1) is involved in IgA nephropathy (IgAN) pathogenesis. To reflect racial differences in clinical characteristics, we assessed disease- and race-specific heterogeneity in the O-glycosylation of the IgA1 hinge region (HR). We determined serum Gd-IgA1 levels in Caucasians (healthy controls [HCs], n = 31; IgAN patients, n = 63) and Asians (HCs, n = 20; IgAN patients, n = 60) and analyzed profiles of serum IgA1 HR O-glycoforms. Elevated serum Gd-IgA1 levels and reduced number of Gal residues per HR were observed in Caucasians. Reduced number of N-acetylgalactosamine (GalNAc) residues per HR and elevated relative abundance of IgA1 with three HR O-glycans were common features in IgAN patients; these features were associated with elevated blood pressure and reduced renal function. We speculate that the mechanisms underlying the reduced GalNAc content in IgA1 HR may be relevant to IgAN pathogenesis.

Original languageEnglish
Article number105223
JournaliScience
Volume25
Issue number11
DOIs
Publication statusPublished - 18-11-2022

All Science Journal Classification (ASJC) codes

  • General

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