Serum Under-galactosylated IgA1 is Increased in Japanese Patients with IgA Nephropathy

Background: Immunoglobulin A nephropathy (IgAN) is characterized by an aberrant structure of O-glycans in the IgA1 hinge region. Recently, under-galactosylated IgA1 has been found to be increased in Caucasian IgAN patients. Thus, we examined this in Japanese IgAN patients.

Methods: An enzyme-linked immunosorbent assay of binding between Helix aspersa (HAA) and serum IgA was performed in Japanese IgAN patients and the HAA-IgA binding levels were compared among IgAN patients (n = 41), patients with other forms of kidney disease (OKD, n = 43) and healthy controls (n = 38). The clinicopathological severity of IgAN was then analysed between patients with high and low HAA-IgA binding levels. The levels were also compared in 11 patients before and after the combination of tonsillectomy and steroid pulse therapy. Furthermore, we examined the O-glycan structure of IgA1 hinge glycopeptides by mass spectrometry (MS).

Results: The HAA-IgA binding levels were significantly higher in IgAN patients compared with either healthy controls (P = 0.0025) or those with OKD (P = 0.016). To reflect the absolute level of under-galactosylated IgA, we multiplied the HAA-IgA binding level by the serum IgA concentration to produce an indicative value. The specificity and sensitivity of this value were 89% and 66%, respectively. MS showed that peak distribution of IgA1 hinge glycopeptides was shifted to smaller molecular weights in high HAA-IgA-binding IgAN patients. There was no correlation between the HAA-IgA binding level and either disease severity or the use of combination therapy.

Conclusions: HAA-IgA binding is significantly increased in Japanese IgAN patients. This potential IgAN marker is not affected by disease severity or therapeutic intervention.