Quantitative change of IgA hinge O-glycan composition is a novel marker of therapeutic responses of IgA nephropathy

Aberrant O-glycosylation in the hinge region of serum IgA is suggested to be involved in the pathogenesis of IgA nephropathy (IgAN), because the hypoglycosylation including N-acetylneuraminic acid or galactose has been reported in the mucin-type O-glycan of the hinge portion (HP) of IgA deposited in the IgAN patients’ kidney. These aberrant glycosylation has been assessed in most of the previous reports by qualitative but not quantitative methods. In the present study, the molar ratios of GalNAc or Gal to HP were analyzed for serum IgA from IgAN patients. The GalNAc/HP ratio was increased in the patients who achieved remission after a combination therapy of tonsillectomy and intravenous corticosteroid, suggesting any non-innate factors to affect the IgA O-glycosylation in IgAN that is thought to be inherently determined. Furthermore, the O-glycosylation status was different among three groups: IgAN patients in the pretreatment stage, IgAN patients in the remission stage after treatment and healthy controls. These results indicated that aberrant O-glycosylation of serum IgA in the IgAN patients would be inherently present and, to some extent, affected by therapeutic intervention. Finally, the quantitative change of O-glycan composition is a novel marker of therapeutic response of IgAN.

► Quantitative analysis of IgA hinge O-glycan composition in IgA nephropathy (IgAN).
► Quantitative change of IgA hinge O-glycan composition is a therapeutic marker in IgAN.
► Successful intervention could modify the inherently-affected aberrant glycosylation.