Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1.
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.
Hiki
Yoshiyuki
Y
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
Takahashi
Kazuo
K
Shimozato
Sachiko
S
Odani
Hiroko
H
Yamamoto
Kouichirou
K
Tomita
Makoto
M
Hasegawa
Midori
M
Murakami
Kazutaka
K
Nabeshima
Kunihiro
K
Nakai
Shigeru
S
Fujita
Yoshiroh
Y
Ishida
Isao
I
Iwase
Hitoo
H
Sugiyama
Satoshi
S
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
D000906:Antibodies; D001212:Asialoglycoproteins; D007070:Immunoglobulin A