title: Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1.
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.
authors.affiliation: Division of Nephrology, Department of Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. yyhiki@fujita-hu.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hiki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Shimozato
authors.forename: Hiroko
authors.initials: H
authors.lastname: Odani
authors.forename: Kouichirou
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Tomita
authors.forename: Midori
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Murakami
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nabeshima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nakai
authors.forename: Yoshiroh
authors.initials: Y
authors.lastname: Fujita
authors.forename: Isao
authors.initials: I
authors.lastname: Ishida
authors.forename: Hitoo
authors.initials: H
authors.lastname: Iwase
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001212:Asialoglycoproteins / Q000276:immunology / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron
chemical_list: D000906:Antibodies; D001212:Asialoglycoproteins; D007070:Immunoglobulin A