杉山　斉    Department   Kawasaki college of Health Professions  ,    Position   Professor
Article types	原著
Language	English
Peer review	Peer reviewed
Title	Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray.
Journal	Formal name：American journal of nephrology Abbreviation：Am J Nephrol ISSN code：14219670/02508095
Domestic / Foregin	Foregin
Volume, Issue, Page	53(1),pp.10-20
Author and coauthor	Onishi Yasuhiro, Mise Koki, Kawakita Chieko, Uchida Haruhito A, Sugiyama Hitoshi, Sugawara Ryosuke, Yamaguchi Satoshi, Yoshida Michihiro, Mitsuhashi Toshiharu, Yamada Masao, Hirabayashi Jun, Wada Jun
Publication date	2022
Summary	INTRODUCTION:The pathogenic roles of aberrantly glycosylated IgA1 have been reported. However, it is unexplored whether the profiling of urinary glycans contributes to the diagnosis of IgAN.METHODS:We conducted a retrospective study enrolling 493 patients who underwent renal biopsy at Okayama University Hospital between December 2010 and September 2017. We performed lectin microarray in urine samples and investigated whether c-statistics of the reference standard diagnosis model employing hematuria, proteinuria, and serum IgA were improved by adding the urinary glycan intensity.RESULTS:Among 45 lectins, 3 lectins showed a significant improvement of the models: Amaranthus caudatus lectin (ACA) with the difference of c-statistics 0.038 (95% CI: 0.019-0.058, p < 0.001), Agaricus bisporus lectin (ABA) 0.035 (95% CI: 0.015-0.055, p < 0.001), and Maackia amurensis lectin (MAH) 0.035 (95% CI: 0.015-0.054, p < 0.001). In 3 lectins, each signal plus reference standard showed good reclassification (category-free NRI and relative IDI) and good model fitting associated with the improvement of AIC and BIC. Stratified by eGFR, the discriminatory ability of ACA plus reference standard was maintained, suggesting the robust renal function-independent diagnostic performance of ACA. By decision curve analysis, there was a 3.45% net benefit by adding urinary glycan intensity of ACA to the reference standard at the predefined threshold probability of 40%.CONCLUSIONS: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 analysis by ACA is a useful and robust noninvasive strategy for the diagnosis of IgAN.
DOI	10.1159/000520998
PMID	34965524