# Longitudinal changes in the abundance of IgA1 O- and N-glycoforms in IgA nephropathy

## TL;DR

This study tracks changes in specific sugar structures on IgA1 antibodies in IgA nephropathy patients undergoing different treatments.

## Contribution

The study reveals treatment-specific longitudinal changes in IgA1 glycoforms, particularly in the T-CST group.

## Key findings

- The abundance of a specific IgA1 O-glycoform decreased only in the T-CST group post-treatment.
- Fucosylated N-glycan abundance increased in IgAN patients and decreased only in the T-CST group after treatment.
- Changes in glycoform abundance were not observed in the CST, CO, or ORD groups.

## Abstract

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis. Elevation in the blood levels of aberrantly glycosylated IgA1 is a crucial initial step in IgAN pathogenesis. Here, we aimed to determine the longitudinal changes in the serum levels of IgA1 O- and N-glycoforms in patients with IgAN receiving different treatments.

We enrolled Japanese patients diagnosed with primary IgAN: 10 patients who underwent tonsillectomy and corticosteroid therapy (T-CST), 7 who received corticosteroid therapy (CST), 8 who received conservative therapy (CO), and 5 with other renal diseases who received corticosteroid therapy (ORD) as disease controls. IgA was purified from patient sera collected at diagnosis and post-treatment. After sample preparation, O-glycoforms of the hinge region (HR) and N-glycoforms of the fragment crystallizable region were analyzed using high-resolution mass spectrometry (MS).

The MS analysis of O-glycoforms of IgA1 showed that the relative abundance of IgA1 with 3GalNAc3Gal, which we previously identified as a characteristic IgA1 O-glycoform in IgAN, decreased post-treatment only in the T-CST group (P = 0.0195). Regarding N-glycoforms, the relative abundance of fucosylated N-glycan at asparagine (Asn)340 increased in the IgAN group compared with that in the ORD group (P = 0.0189) and decreased post-treatment only in the T-CST group (P = 0.0195).

The MS analysis of O- and N-glycoforms of IgA1 revealed substantial changes in their abundance in the T-CST group but not in the CST, CO, and ORD groups. Our study provides new insights into how specific treatments alter the IgA1 glycoform abundance.

The online version contains supplementary material available at 10.1007/s10157-025-02659-y.