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
Affiliations
Yukako Ohyama
Department of Biomedical Molecular Sciences, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan; Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Hisateru Yamaguchi
Department of Nursing, Yokkaichi Nursing and Medical Care University, Yokkaichi, Mie 512-8045, Japan
Soshiro Ogata
Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Suita, Osaka 564-8565, Japan
Samantha Chiurlia
University of Bari and Schena Foundation, Valenzano, Bari 70010, Italy
Sharon N. Cox
University of Bari and Schena Foundation, Valenzano, Bari 70010, Italy
Nikoletta-Maria Kouri
Department of Nephrology, Aristotle University of Thessaloniki, Thessaloniki, 54642, Greece
Maria J. Stangou
Department of Nephrology, Aristotle University of Thessaloniki, Thessaloniki, 54642, Greece
Kazuki Nakajima
Institute for Glyco-core Research, Gifu University, Gifu, Gifu 501-1193, Japan
Hiroki Hayashi
Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Daijo Inaguma
Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Midori Hasegawa
Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Yukio Yuzawa
Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Naotake Tsuboi
Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Matthew B. Renfrow
Departments of Biochemistry and Molecular Genetics and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jan Novak
Departments of Biochemistry and Molecular Genetics and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Aikaterini A. Papagianni
Department of Nephrology, Aristotle University of Thessaloniki, Thessaloniki, 54642, Greece
Francesco P. Schena
University of Bari and Schena Foundation, Valenzano, Bari 70010, Italy; Corresponding author
Kazuo Takahashi
Department of Biomedical Molecular Sciences, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan; Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan; Corresponding author
Summary: 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.
