Evaluation of IgA1 O-glycosylation in Henoch-Schönlein Purpura Nephritis Using Mass Spectrometry

Glomerular deposition of IgA1 is a common feature of Henoch-Schönlein purpura nephritis (HSPN) and is indistinguishable from that seen in IgA nephropathy (IgAN). Serum IgA1 is abnormally O-glycosylated in IgA nephropathy, which may contribute to the development of glomerular injury. Abnormal O-glycosylated IgA1 was also detected in HSPN using lectin enzyme-linked immunosorbent assay; however, this method cannot provide the exact structural information of O-glycans. Mass spectrometry is an effective means of quantification of O-glycans, and there is no report to evaluate IgA1 O-glycans in HSPN using mass spectrometry. We investigated O-glycosylation profile in serum IgA1 from 7 HSPN recipients, 26 IgAN recipients, 25 recipients with other kidney diseases (OKDs), and 26 normal healthy donors using mass spectrometry. Of the 14 GalNac-Gal combinations detected using mass spectrometry, the percentage of the only 6GalNAc-2Gal combination was significantly different between HSPN and IgAN. The percentage of GalNAc 3 in HSPN recipients was significantly higher than that in OKDs recipients and healthy donors (P = .0027 and P < .0001, respectively). Inversely, the percentage of GalNAc 5 in HSPN recipients was significantly lower than that in OKDs recipients and healthy donors (P = .0008, P < .0001, respectively). Moreover, the Gal content and the Gal/GalNAc ratio of HSPN recipients were significantly lower than OKDs recipients and healthy donors. Examination of Henoch-Schönlein purpura recipients revealed that the number of GalNAc fell and the Gal attachment to GalNAc was reduced compared to other kidney diseases and healthy donors. The IgA1 O-glycosylation profile of HSPN was very similar to that of IgAN. •This article evaluates IgA1 O-glycosylation profile using mass spectrometry (MALDI–TOF MS).•We compared Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN).•IgA1 O-glycosylation profiles are common in many respects between HSPN and IgAN.•The amount of GalNAc content in HSPN decreased.•The Gal attachment to GalNAc in HSPN also decreased.