2006 Fiscal Year Final Research Report Summary
Investigations of pathogenesis and therapeutic approach for IgA nephropathy.-A trial of experimental mouse model of glomerular deposition of human IgA-
| Project/Area Number |
16590804
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Fujita Health University |
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Principal Investigator |
HIKI Yoshiyuki Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (20156566)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Satoshi Fujita Health University, School of Medicine, Professor, 医学部, 教授 (50340229)
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| Project Period (FY) |
2004 – 2006
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| Keywords | IgA1 hinge / O-glycans / IgA nephropathy / KM mouse / galactose / sialic acid |
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| Research Abstract |
The KM mouse lacks endogenous genes for immunoglobulins and carries the human entire human IgH locus and the IgLk transgene. Therefore, human IgA1 does not provoke a hetero-immune response. We had observed mesangial IgA deposits in KM mice given desialo-degalacto (DeS/DeGal) IgA1. In this study, the mice were immunized with synthetic IgA1 hinge (glyco-)peptide before administration of DeS/DeGal IgA1, and the effects of the pre-immunization were evaluated. Mice were divided into sHP, 5Ga1NAc-sHP and non-immunization groups. In two pre-immunization groups, KLH-conjugated sHP or KLH-5GalNAc-sHP, which has five GalNAc residues, was subcutaneously given three times every two weeks. Two weeks after the final pre-immunization, DeS/DeGal IgA1 was daily administered for five weeks. Serial serum levels of anti-sHP and anti-IgA1antibodies were evaluated by ELISA. On the day of the last administration of IgA1, renal biopsy was performed. Mesangial IgA deposits were observed in all non-immunized mice. In pre-immunized mice, IgA deposition was not detected in six of 13 sHP mice and one of four 5GalNAc-sHP mice. The intensities of IgA deposits were significantly different between sHP groups and non-immunized (p=0.003) groups. There was a significant inverse correlation between the intensities of IgA deposits and the anti-sHP antibody titers (p=0.016). These results suggest that the anti-IgA1 hinge peptide antibody plays a role in the inhibition of glomerular IgA deposition.
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