NDT Advance Access originally published online on January 4, 2008
Nephrology Dialysis Transplantation 2008 23(6):1931-1939; doi:10.1093/ndt/gfm913
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Serum under-galactosylated IgA1 is increased in Japanese patients with IgA nephropathy
Department of Nephrology, Fujita Health University, School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
Correspondence and offprint requests to: Yoshiyuki Hiki, Department of Nephrology, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. Tel: +81-562-93-9245; Fax: +81-562-93-1830; E-mail: yyhiki{at}fujita-hu.ac.jp
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Abstract |
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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.
Keywords: IgA1; HAA; GalNAc; galactose; neuraminic acid
Received for publication: 21. 8.07
Accepted in revised form: 3.12.07