TY - JOUR
T1 - Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1
AU - Hiki, Yoshiyuki
AU - Takahashi, Kazuo
AU - Shimozato, Sachiko
AU - Odani, Hiroko
AU - Yamamoto, Kouichirou
AU - Tomita, Makoto
AU - Hasegawa, Midori
AU - Murakami, Kazutaka
AU - Nabeshima, Kunihiro
AU - Nakai, Shigeru
AU - Fujita, Yoshiroh
AU - Ishida, Isao
AU - Iwase, Hitoo
AU - Sugiyama, Satoshi
N1 - Funding Information:
Authors thank Dr. Yutaka Kobayashi of Akebono Hospital for giving us valuable suggestions and Professor K. Ajisaka of Niigata University of Pharmacy and Applied Life Sciences for providing β1,3-galactosidase. Mses. M. Itoh, I. Matsumoto and K. Inoue contributed to the study with their excellent technical assistance. This work was supported in part by a Grant-in-Aid for the 21st Century Center of Excellence Program of Fujita Health University from the Ministry of Education, Culture, Sports, Sciences, and Technology of Japan, a Grant-in-Aid from The Ministry of Education, Science and Culture of Japan (No1659804) and Fujita Health University Research Foundation.
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
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U2 - 10.1007/s10157-007-0002-9
DO - 10.1007/s10157-007-0002-9
M3 - Article
C2 - 18175057
AN - SCOPUS:38549170130
VL - 12
SP - 20
EP - 27
JO - Clinical and Experimental Nephrology
JF - Clinical and Experimental Nephrology
SN - 1342-1751
IS - 1
ER -