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

doi:10.1016/j.isci.2022.105223

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

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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 language	English
Article number	105223
Journal	iScience
Volume	25
Issue number	11
DOIs	https://doi.org/10.1016/j.isci.2022.105223
Publication status	Published - 18-11-2022

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Ohyama, Y., Yamaguchi, H., Ogata, S., Chiurlia, S., Cox, S. N., Kouri, N. M., Stangou, M. J., Nakajima, K., Hayashi, H., Inaguma, D., Hasegawa, M., Yuzawa, Y., Tsuboi, N., Renfrow, M. B., Novak, J., Papagianni, A. A., Schena, F. P., & Takahashi, K. (2022). Racial heterogeneity of IgA1 hinge-region O-glycoforms in patients with IgA nephropathy. iScience, 25(11), Article 105223. https://doi.org/10.1016/j.isci.2022.105223

@article{49210339a13d466f961ab381e5d74dfe,

title = "Racial heterogeneity of IgA1 hinge-region O-glycoforms in patients with IgA nephropathy",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = nov,

day = "18",

doi = "10.1016/j.isci.2022.105223",

language = "English",

volume = "25",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "11",

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Ohyama, Y, Yamaguchi, H, Ogata, S, Chiurlia, S, Cox, SN, Kouri, NM, Stangou, MJ, Nakajima, K, Hayashi, H , Inaguma, D , Hasegawa, M , Yuzawa, Y , Tsuboi, N, Renfrow, MB, Novak, J, Papagianni, AA, Schena, FP & Takahashi, K 2022, 'Racial heterogeneity of IgA1 hinge-region O-glycoforms in patients with IgA nephropathy', iScience, vol. 25, no. 11, 105223. https://doi.org/10.1016/j.isci.2022.105223

TY - JOUR

T1 - Racial heterogeneity of IgA1 hinge-region O-glycoforms in patients with IgA nephropathy

AU - Ohyama, Yukako

AU - Yamaguchi, Hisateru

AU - Ogata, Soshiro

AU - Chiurlia, Samantha

AU - Cox, Sharon N.

AU - Kouri, Nikoletta Maria

AU - Stangou, Maria J.

AU - Nakajima, Kazuki

AU - Hayashi, Hiroki

AU - Inaguma, Daijo

AU - Hasegawa, Midori

AU - Yuzawa, Yukio

AU - Tsuboi, Naotake

AU - Renfrow, Matthew B.

AU - Novak, Jan

AU - Papagianni, Aikaterini A.

AU - Schena, Francesco P.

AU - Takahashi, Kazuo

PY - 2022/11/18

Y1 - 2022/11/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85139846932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85139846932&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2022.105223

DO - 10.1016/j.isci.2022.105223

M3 - Article

AN - SCOPUS:85139846932

SN - 2589-0042

VL - 25

JO - iScience

JF - iScience

IS - 11

M1 - 105223

ER -

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

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