Suppression of experimental membranous glomerulonephritis in rats by an anti-MHC class II antibody.
BACKGROUND
We previously reported that idiopathic membranous nephropathy (IMN) strongly correlated with HLA-DRB1*1501-DRB5*0101-DQAI*0102-DQB1* 0602, a specific haplotype of human major histocompatibility complex (MHC), in Japanese patients. To investigate the role of MHC in the development of rat Heymann nephritis (HN), an animal model of membranous nephropathy, a monoclonal antibody (mAb) specific to rat MHC class II antigen (RT1B) was administered, and its effectiveness in inhibiting HN was assessed.


METHODS
Active HN was induced in HN-sensitive Lewis rats by administering brush border proteins of rat proximal uriniferous tubules (FX1A). Rats were divided into four groups: rats treated with 1,000 micorg anti-rat MHC class II mAb, rats treated with 100 microg anti-rat MHC class II mAb, rats treated with murine myeloma IgG, and rats that did not receive either FX1A or any other mAb. We examined the differences in 24-hour urinary protein excretion and serum alloantibody titers against FX1A between groups at different time intervals, and the histologic features of kidneys at the end of the study.


RESULTS
HN was induced in Lewis rats by inoculation with FX1A antigen. Administration of anti-MHC class II mAb successfully lowered urinary proteins, production of anti-FX1A alloantibodies, and the development of glomerular lesions in a dose-dependent manner.


CONCLUSIONS
The present results demonstrated that the MHC class II molecule itself is directly involved in the pathogenesis of HN, and suggest that this therapy would be any better (or less toxic) than nonselective immunosuppressants in the treatment of IMN.
Hasegawa
Y
Y
Fukuoka University Hospital Kidney Center, Fukuoka, Japan. 964rsr@lycos.ne.jp
Kaneoka
H
H
Tanaka
T
T
Ogahara
S
S
Matsumae
T
T
Noda
R
R
Yoshitake
K
K
Murata
T
T
Naito
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D015433:Glomerulonephritis, Membranous / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D026541:Heymann Nephritis Antigenic Complex; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D007668:Kidney / Q000473:pathology; D008562:Membrane Glycoproteins / Q000008:administration & dosage; D051379:Mice; D008854:Microscopy, Electron; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D026541:Heymann Nephritis Antigenic Complex; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D008562:Membrane Glycoproteins