Difference in IgA1 O-glycosylation between IgA deposition donors and IgA nephropathy recipients

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, and disease recurrence often occurs after transplantation. On the other hands, Asymptomatic IgA deposition (IgAD) is occasionally observed in donated kidney. It is recognized that IgAD does not progress to IgAN, but the mechanism has not demonstrated yet. In IgAN, aberrant IgA1 O-glycan structure in the hinge region (HR) of serum IgA is suggested as one of the most convincing key mediators. However, little is known about IgA1 O-glycan structure in IgAD patients. Herein, we investigated the prevalence of IgAD in living renal transplant donors in our cohort. IgAD was observed in 21(13.0%) among 161 renal transplant donors and have statistically significant blood relationship with IgAN recipients (28.6% in relatives vs. 9.8% in non-relatives, respectively; p = 0.0073). Next, we evaluated the IgA1 O-glycan structure of serum IgA from IgAN recipients (n = 26), IgAD donors (n = 17), and non-IgAD helthy donors (n = 27) using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The numbers of GalNAc and Gal and the Gal/GalNAc ratio in the HR of the IgAN recipients had significantly lower comparing to the IgAD and non-IgAD healthy donors. The decreased Gal/GalNAc ratio in IgAN recipients means the increased ratio of galactose-deficient IgA1. To the best of our knowledge, this is the first report to compare the O-glycan structures in IgAN recipients and IgAD donors using MALDI-TOF MS. We concluded that IgAD was more common in IgAN related donors. Overall, decreased GalNAc and Gal contents in HR could play a material pathogenic role in IgAN.