Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1

Yoshiyuki Hiki, Kazuo Takahashi, Sachiko Shimozato, Hiroko Odani, Kouichirou Yamamoto, Makoto Tomita, Midori Hasegawa, Kazutaka Murakami, Kunihiro Nabeshima, Shigeru Nakai, Yoshiroh Fujita, Isao Ishida, Hitoo Iwase, Satoshi Sugiyama

研究成果: Article

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Background: The KM mouse lacks endogenous genes for immunoglobulins and carries the 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. Methods: 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, 5GalNAc-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 2 weeks. Two weeks after the final pre-immunization, DeS/DeGal IgA1 was administered daily for 5 weeks. Serial serum levels of anti-sHP and anti-IgA1 antibodies were evaluated by ELISA. On the day of the last administration of IgA1, renal biopsy was performed. Results: Mesangial IgA deposits were observed in all non-immunized mice. In pre-immunized mice, IgA deposition was not detected in 6 of 13 sHP mice and 1 of 4 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). Conclusions: These results suggest that the anti-IgA1 hinge peptide antibody plays a role in the inhibition of glomerular IgA deposition.

元の言語English
ページ(範囲)20-27
ページ数8
ジャーナルClinical and Experimental Nephrology
12
発行部数1
DOI
出版物ステータスPublished - 01-02-2008

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

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    Hiki, Y., Takahashi, K., Shimozato, S., Odani, H., Yamamoto, K., Tomita, M., Hasegawa, M., Murakami, K., Nabeshima, K., Nakai, S., Fujita, Y., Ishida, I., Iwase, H., & Sugiyama, S. (2008). Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1. Clinical and Experimental Nephrology, 12(1), 20-27. https://doi.org/10.1007/s10157-007-0002-9