The Analysis of aberrant glycosylation of IgA and B cells secreting those IgAs in IgA Nephropathy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461232
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Juntendo University
• Principal Investigator: KIHARA Masao 順天堂大学, 医学部, 助教 (50512604)
• Co-Investigator(Kenkyū-buntansha): TOMINO Yasuhiko 順天堂大学, 医学部, 教授 (60130077) ; SUZUKI Hitoshi 順天堂大学, 医学部, 准教授 (10468572) ; SUZUKI Yusuke 順天堂大学, 医学部, 准教授 (70372935) ; NAKATA Junichiro 順天堂大学, 医学部, 助教 (20365638)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: IgA腎症 / 糖鎖不全

Outline of Final Research Achievements

O-linked glycans of IgA1 from IgAN patients revealed an aberrant glycosylation status characterized by diminished galactosylation. Implantation of transfectoma cells secreting an IgA derived from ddY mice (ddY-IgAN hybridoma) induced glomerular lesion resembling human IgAN in BALB/c mice. Among the six GalNAc-Ts expressed in human B cells, GalNAc-T2 exhibited the highest catalytic activity in transferring GalNAc to a synthetic peptide from the hinge region of human IgA1. We observed that GalNAc-T2 mRNA expression was higher in ddY-IgA N hybridoma than ddY-deriver hybridoma not inducing IgAN. Thus, more O-glycosylated ddY-IgAN hybridoma will be generated by either enhancing the expression of GalNAc-T2 through transfection with plasmids encoding GalNAc-T2 cDNA. The extent of O-glycosylation from the hinge region of secreted IgAs will be verified by MALDI-TOF MS, and cells secreting ddY-IgAN hybridoma variants will be implanted into BALB/c mice to test their nephritogenicity.

Free Research Field

腎臓内科学