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Abstract: SA-PO840

Longitudinal Changes in IgA1 O- and N-Glycoforms in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Hirayama, Masaya, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
  • Ohyama, Yukako, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
  • Tsuji, Yudai, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
  • Tsuboi, Naotake, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
  • Takahashi, Kazuo, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
Background

An increased level of circulating aberrantly glycosylated IgA1 has been considered a significant initial step in the pathogenesis of IgAN. Recently, the molecular features of IgA1 O- and N-glycoforms in patients with IgAN have been reported using high-resolution mass spectrometry (HRMS). While specific glycopeptides have been reported to be a possible predictor of IgAN and glomerular function, it is still largely unclear how the glycosylation of IgA1 changes according to treatment. In this study, we aimed to determine the difference in IgA1 O- and N-glycoform changes between different treatment groups at two time points: at diagnosis and post-treatment, using a prospective cohort enrolled at Fujita Health University Hospital.

Methods

We registered patients diagnosed with primary IgAN by renal biopsy during 2017–2019. Ten patients who received tonsillectomy and corticosteroid therapy (T-CST group), eight patients who received conservative therapy (CO group), and five patients with other renal diseases who were treated with corticosteroid therapy (ORD group) were enrolled. IgA was purified from the serum of patients at two time points (at diagnosis and post-treatment). After neuraminidase treatment, O-glycoforms of the hinge region (HR) and N-glycoforms of the Fc region were analyzed using online liquid chromatography-HRMS.

Results

The mass spectrometry analysis of O-glycoforms of IgA1 HR showed that the number of N-acetylgalactosamine in the IgA1 HR was significantly increased only in the T-CST group from diagnosis to post-treatment (P = 0.0325), while the number of galactose in the IgA1 HR remained unchanged in all groups. The mass spectrometry analysis of N-glycoforms also showed several changes only in the T-CST group. In asparagine (Asn)340, at post-treatment, there was a significant increase in the relative abundance of the oligomannose-type (P = 0.0020) and a significant decrease in the galactosylation of the tri-antennary-type (P = 0.0098); whereas in Asn144, there was a significant decrease in the relative abundance of fucosylated glycan (P = 0.0195).

Conclusion

This study found that some glycoforms previously reported to be characteristics of IgAN were altered only in the T-CST group of IgAN but not in the CO group of IgAN or the ORD group. The detection of O- and N-glycoform alterations may be IgAN-specific biomarkers of disease activity.

Funding

  • Government Support – Non-U.S.