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Abstract: PO1591

Identification of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Onishi, Yasuhiro, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Mise, Koki, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Uchida, Haruhito A., Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Sugiyama, Hitoshi, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Wada, Jun, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Background

IgA nephropathy (IgAN) is the most common form of glomerulonephritis and the pathogenic roles of aberrantly glycosylated IgA1 have been reported. The glycan abnormalities are mediated by the alterations of glycan processing enzymes, such as decreased activity of β-1,3-galactosyltransferase (C1GALT1). However, it is unexplored whether the detection of urinary glycosylation changes contributes to the diagnosis of IgAN.

Methods

We measured the urinary glycan signals bound to 45 lectins on LecChip in the 493 patients with renal biopsy-proven kidney diseases at Okayama University Hospital from December 2010 to September 2017. To evaluate the diagnostic performance, we added the urinary glycan signals to the diagnosis model with the reference standard, i.e., the presence of hematuria, 24 hr urinary protein excretion, and concentration of serum IgA.

Results

The inclusion of 6 lectins showed a significant improvement of the models; Amaranthus Caudatus (ACA) with the difference of AUC 0.038 [95%CI, 0.019 - 0.058, P < 0.001], Agaricus Bisporus (ABA) 0.035 [95%CI, 0.015 - 0.055, P < 0.001], Maackia Amurensis (MAH) 0.035 [95%CI, 0.015 - 0.054, P < 0.001], Maackia Amurensis (MAH) 0.035 [95%CI, 0.015 - 0.054, P < 0.001], Maclura Pomifera (MPA) 0.021 [95%Cl, 0.006 - 0.037, P = 0.006], Jacalin 0.019 [95%Cl, 0.004 - 0.034, P = 0.012], and Lycopersicon Esculentum (LEL) 0.016 [95%Cl, 0 - 0.032, P = 0.045]. All 6 lectins demonstrated reduced signals in IgAN patients and 3 lectins (ACA, ABA, MAH) showed false discovery rate (FDR) below 0.05. In 3 lectins, each signal plus reference standard showed good model fitting associated with the improvement of AIC. By decision curve analysis, there was a 3.45% net benefit by adding urinary glycan signals to ACA at the pre-defined threshold probability of 40%.

Conclusion

The reduction of Gal(β1-3)GalNAc (T-antigen), Sia(α2-3)Gal(β1-3)GalNAc (Sialyl T), and Sia(α2-3)Gal(β1-3)Sia(α2-6)GalNAc (disialyl-T) was suggested by binding specificities of 3 lectins. C1GALT1 and COSMC were responsible for the biosynthesis of these glycans, and they were known to be downregulated in IgAN. The urinary glycan profile may be useful for the identification of diagnostic marker for IgA nephropathy.

Funding

  • Private Foundation Support