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.
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 IgANpatients. Thus, we examined this in Japanese IgANpatients. METHODS: An enzyme-linked immunosorbent assay of binding between Helix aspersa (HAA) and serum IgA was performed in Japanese IgANpatients and the HAA-IgA binding levels were compared among IgANpatients (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 IgANpatients 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 IgANpatients. 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 IgANpatients. This potential IgAN marker is not affected by disease severity or therapeutic intervention.
Authors: Michelle M Gomes; Hitoshi Suzuki; Monica T Brooks; Milan Tomana; Zina Moldoveanu; Jiri Mestecky; Bruce A Julian; Jan Novak; Andrew B Herr Journal: Biochemistry Date: 2010-07-13 Impact factor: 3.162
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Authors: Margaret Colleen Hastings; Zina Moldoveanu; Hitoshi Suzuki; Francois Berthoux; Bruce A Julian; John T Sanders; Matthew B Renfrow; Jan Novak; Robert J Wyatt Journal: Expert Opin Med Diagn Date: 2013-11
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