Kidney Week

Abstract: PO1795

Racial Heterogeneity of IgA₁ Hinge Region O-Glycoforms in Patients with IgA Nephropathy

Session Information

• Glomerular Diseases: IgA, C3G, and FSGS
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Ohyama, Yukako, Fujita Health University, Toyoake, Aichi, Japan

Yukako Ohyama,

• Chiurlia, Samantha, University of Bari and Schena Foundation, Valenzano, Italy

Samantha Chiurlia,

• Cox, Sharon N., University of Bari and Schena Foundation, Valenzano, Italy

Sharon N. Cox,

• Kouri, Nikoletta-Maria, Aristotle University of Thessaloniki, Thessaloniki, Greece

Nikoletta-Maria Kouri,

• Stangou, Maria J., Aristotle University of Thessaloniki, Thessaloniki, Greece

Maria J. Stangou,

• Yamaguchi, Hisateru, Fujita Health University, Toyoake, Aichi, Japan

Hisateru Yamaguchi,

• Nakajima, Kazuki, Fujita Health University, Toyoake, Aichi, Japan

Kazuki Nakajima,

• Inaguma, Daijo, Fujita Health University, Toyoake, Aichi, Japan

Daijo Inaguma,

• Hasegawa, Midori, Fujita Health University, Toyoake, Aichi, Japan

Midori Hasegawa,

• Yuzawa, Yukio, Fujita Health University, Toyoake, Aichi, Japan

Yukio Yuzawa,

• Tsuboi, Naotake, Fujita Health University, Toyoake, Aichi, Japan

Naotake Tsuboi,

• Papagianni, Aikaterini A., Aristotle University of Thessaloniki, Thessaloniki, Greece

Aikaterini A. Papagianni,

• Schena, Francesco Paolo, University of Bari and Schena Foundation, Valenzano, Italy

Francesco Paolo Schena,

• Takahashi, Kazuo, Fujita Health University, Toyoake, Aichi, Japan

Kazuo Takahashi,

Background

IgA1 with galactose (Gal)-deficient hinge region (HR) O-glycans (Gd-IgA1) plays a crucial role in the pathogenesis of IgA nephropathy (IgAN). The microRNAs, named let7b and miR-148b, which affect IgA1 HR O-glycosylation, showed differences in serum levels between Caucasians and Asians, suggesting a racial difference in HR O-glycosylation. To understand race-specific IgA1 HR O-glycoform heterogeneity at the molecular level, we compared Greek and Japanese profiles of IgA1 HR O-glycoforms in patients with IgAN.

Methods

IgA1 from sera of 10 Japanese healthy controls (J-HC), 36 Japanese IgAN patients (J-IgAN), 16 Greek HCs (G-HC), and 23 Greek IgAN patients (G-IgAN) were purified through affinity chromatography. After neuraminidase and trypsin digestion, samples underwent liquid chromatography-high-resolution mass spectrometry, and individual profiles of IgA1 HR O-glycoform were quantitatively analyzed. The amounts of N-acetylglucosamine (GalNAc) and Gal were shown as the median number of sugar moieties per HR.

Results

Twelve variants of the IgA1 HR O-glycopeptide were detected in both HCs and IgAN patients. The disease-specific IgA1 HR O-glycoforms were 3GalNAc3Gal in Japanese (P < 0.001) and 3GalNAc2Gal (P = 0.007) and 5GalNAc3Gal (P = 0.043) in Greek individuals. The amount of GalNAc per HR showed a common tendency to decrease in patients from both racial groups, compared with healthy subjects, and was more prominent in G-IgAN than in J-IgAN (P = 0.027). The amount of Gal per HR decreased in the following order: J-IgAN, G-HC, J-HC, and G-IgAN, and was significantly lower in G-IgAN than in J-IgAN (P = 0.001).

Conclusion

The amount of GalNAc per HR decreased in patients of both races and was prominent in G-IgAN. The difference in GalNAc levels between G-IgAN and J-IgAN showed correspondence with previously reported serum let-7b racial differences, which were associated with the regulation of the initial glycosylation of HR. Further studies regarding upstream factors and changes downstream of GalNAc glycosylation are required to understand the pathogenesis of IgAN.

Funding

• Government Support - Non-U.S.