BACKGROUND: Although many reports have described the abnormal structures of O-glycan in the IgA1 hinge region in IgA nephropathy (IgAN), the specific glycopeptide that can be used as a diagnostic biomarker for IgAN has not yet been identified. To pursue this diagnostic approach, we used mass spectrometric analysis to search for specific structures in IgA1 hinge glycopeptides in 30 IgAN patients contrasted with 30 healthy controls. METHOD: IgA1 hinge glycopeptides were individually purified from the sera of 30 biopsy-proven IgAN patients and 30 healthy controls. The structure of each glycopeptide was analyzed by ion trap mass spectrometry. Sugar conformations in each glycopeptide were estimated by collision-induced dissociation tandem mass spectrometry. Furthermore, to search for specific O-glycans in IgAN patients with a statistical significance, the identified hinge glycopeptides were analyzed by Fisher exact test. RESULT: A total of 57 hinge glycopeptides were identified from each of the 2 sample groups. Among the structures of the hinge glycopeptides identified, statistical significance was found for 6 glycopeptides (O-glycan compositions were 33-mer hinge core peptides + xGalNAc + yGal + zNeu5Ac; x:y:z = 5:3:3, 5:3:0, 5:2:1, 4:2:2, 3:1:1, 3:1:0) by Fisher exact test (p<0.05). In these 6 O-glycan compositions, 3 compositions (x:y:z = 4:2:2, 3:1:1, 3:1:0) were only observed in IgAN patients and were absent in the 30 controls. CONCLUSION: Statistically specific O-glycans were identified in 30 IgAN patients compared with 30 controls. These results open the possibility for preparation of lectin and/or antibodies binding to specific glycopeptides in IgAN.
BACKGROUND: Although many reports have described the abnormal structures of O-glycan in the IgA1 hinge region in IgA nephropathy (IgAN), the specific glycopeptide that can be used as a diagnostic biomarker for IgAN has not yet been identified. To pursue this diagnostic approach, we used mass spectrometric analysis to search for specific structures in IgA1 hinge glycopeptides in 30 IgANpatients contrasted with 30 healthy controls. METHOD:IgA1 hinge glycopeptides were individually purified from the sera of 30 biopsy-proven IgANpatients and 30 healthy controls. The structure of each glycopeptide was analyzed by ion trap mass spectrometry. Sugar conformations in each glycopeptide were estimated by collision-induced dissociation tandem mass spectrometry. Furthermore, to search for specific O-glycans in IgANpatients with a statistical significance, the identified hinge glycopeptides were analyzed by Fisher exact test. RESULT: A total of 57 hinge glycopeptides were identified from each of the 2 sample groups. Among the structures of the hinge glycopeptides identified, statistical significance was found for 6 glycopeptides (O-glycan compositions were 33-mer hinge core peptides + xGalNAc + yGal + zNeu5Ac; x:y:z = 5:3:3, 5:3:0, 5:2:1, 4:2:2, 3:1:1, 3:1:0) by Fisher exact test (p<0.05). In these 6 O-glycan compositions, 3 compositions (x:y:z = 4:2:2, 3:1:1, 3:1:0) were only observed in IgANpatients and were absent in the 30 controls. CONCLUSION: Statistically specific O-glycans were identified in 30 IgANpatients compared with 30 controls. These results open the possibility for preparation of lectin and/or antibodies binding to specific glycopeptides in IgAN.
Authors: Hitoshi Suzuki; Krzysztof Kiryluk; Jan Novak; Zina Moldoveanu; Andrew B Herr; Matthew B Renfrow; Robert J Wyatt; Francesco Scolari; Jiri Mestecky; Ali G Gharavi; Bruce A Julian Journal: J Am Soc Nephrol Date: 2011-09-23 Impact factor: 10.121
Authors: Francois Berthoux; Hitoshi Suzuki; Lise Thibaudin; Hiroyuki Yanagawa; Nicolas Maillard; Christophe Mariat; Yasuhiko Tomino; Bruce A Julian; Jan Novak Journal: J Am Soc Nephrol Date: 2012-08-16 Impact factor: 10.121
Authors: Sylvain Lehoux; Rongjuan Mi; Rajindra P Aryal; Yingchun Wang; Katrine T-B G Schjoldager; Henrik Clausen; Irma van Die; Yoosun Han; Arlene B Chapman; Richard D Cummings; Tongzhong Ju Journal: Mol Cell Proteomics Date: 2014-07-28 Impact factor: 5.911