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

• Published in: iScience 2022-11, Vol.25 (11), p.105223-105223, Article 105223
• Main Authors: Ohyama, Yukako, Yamaguchi, Hisateru, Ogata, Soshiro, Chiurlia, Samantha, Cox, Sharon N., Kouri, Nikoletta-Maria, Stangou, Maria J., Nakajima, Kazuki, Hayashi, Hiroki, Inaguma, Daijo, Hasegawa, Midori, Yuzawa, Yukio, Tsuboi, Naotake, Renfrow, Matthew B., Novak, Jan, Papagianni, Aikaterini A., Schena, Francesco P., Takahashi, Kazuo
• Format: Article
• Language: English
• Subjects: Clinical finding; Pathophysiology; Physiological state
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105223

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. [Display omitted] •Elevated serum Gd-IgA1 is more pronounced in Caucasians than in Asians•Reduced number of IgA1 HR O-glycans is common in IgAN•This feature is associated with reduced kidney function and high BP in IgAN•Specific IgA1 O-glycoforms in IgAN will inform development of new biomarkers Clinical finding; Physiological state; Pathophysiology.