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

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Abstract

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.

Original languageEnglish
Pages (from-to)20-27
Number of pages8
JournalClinical and Experimental Nephrology
Volume12
Issue number1
DOIs
Publication statusPublished - 01-02-2008

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Immunoglobulin A
Peptides
Antibodies
Immunization
Anti-Idiotypic Antibodies
Immunoglobulin Genes
Transgenes
Enzyme-Linked Immunosorbent Assay
Kidney
Biopsy

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

Hiki, Yoshiyuki ; Takahashi, Kazuo ; Shimozato, Sachiko ; Odani, Hiroko ; Yamamoto, Kouichirou ; Tomita, Makoto ; Hasegawa, Midori ; Murakami, Kazutaka ; Nabeshima, Kunihiro ; Nakai, Shigeru ; Fujita, Yoshiroh ; Ishida, Isao ; Iwase, Hitoo ; Sugiyama, Satoshi. / Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1. In: Clinical and Experimental Nephrology. 2008 ; Vol. 12, No. 1. pp. 20-27.
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abstract = "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.",
author = "Yoshiyuki Hiki and Kazuo Takahashi and Sachiko Shimozato and Hiroko Odani and Kouichirou Yamamoto and Makoto Tomita and Midori Hasegawa and Kazutaka Murakami and Kunihiro Nabeshima and Shigeru Nakai and Yoshiroh Fujita and Isao Ishida and Hitoo Iwase and Satoshi Sugiyama",
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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, vol. 12, no. 1, pp. 20-27. https://doi.org/10.1007/s10157-007-0002-9

Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1. / Hiki, Yoshiyuki; Takahashi, Kazuo; Shimozato, Sachiko; Odani, Hiroko; Yamamoto, Kouichirou; Tomita, Makoto; Hasegawa, Midori; Murakami, Kazutaka; Nabeshima, Kunihiro; Nakai, Shigeru; Fujita, Yoshiroh; Ishida, Isao; Iwase, Hitoo; Sugiyama, Satoshi.

In: Clinical and Experimental Nephrology, Vol. 12, No. 1, 01.02.2008, p. 20-27.

Research output: Contribution to journalArticle

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

PY - 2008/2/1

Y1 - 2008/2/1

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

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