Reduction of MPO-ANCA epitopes in SCG/Kj mice by 15-deoxyspergualin treatment restricted by IgG2b associated with crescentic glomerulonephritis.
OBJECTIVE
The MPO-specific antineutrophil cytoplasmic antibodies (MPO-ANCA) are associated with renal failure. Epitopes of MPO-ANCA and immunoglobulin G (IgG) subclass and cytokine levels in the recovery phase were analysed by the administration of 15-deoxyspergualin (DSG) to SCG/Kj mice, which show spontaneous crescentic GN (CrGN).


METHODS
We treated SCG/Kj mice by using DSG and MPO deletion mutants to investigate epitopes of MPO-ANCA associated with renal failure in SCG/Kj mice. After DSG treatment for 30 days, we observed histological changes in a crescentic formation and infiltration of neutrophils and lymphocytes into kidney, cytokines/chemokines and MPO-ANCA epitopes by deletion mutants.


RESULTS
MPO-ANCA were reduced by the administration of DSG, and epitopes of MPO-ANCA, mainly H-6, decreased. Moreover, the IgG2b subclass of the H-6 epitope of MPO-ANCA was greatly decreased by DSG treatment. These observations correlated with a decrease in renal failure and proteinuria, infiltration of neutrophils and lymphocytes into glomeruli, and crescent formation. The CD4/CD8 ratio of splenocytes ranged from 1.68 (0.24) in the non-treated group to 0.90 (0.12) at 100 microg/mouse/day in the DSG-treated group. In addition, elevated levels of IL-12p40, IL-10 and IL-13 in the active phase of CrGN clearly decreased with DSG treatment but not with TNF-alpha. In contrast, the IL-1alpha level increased, and IL-17 and IL-12p70 slightly increased with DSG treatment.


CONCLUSIONS
These results strongly suggest that DSG treatment of SCG/Kj mice leads to the reduction of risk antibodies in IgG2b and normalization of B-cell clones accompanied by recovery of the cytokine and chemokine balance.
Tomizawa
Kazuo
K
Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.
Nagao
Tomokazu
T
Kusunoki
Reina
R
Saiga
Kan
K
Oshima
Masamichi
M
Kobayashi
Kazuo
K
Nakayama
Toshinori
T
Tanokura
Masaru
M
Suzuki
Kazuo
K
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007958:Leukocyte Count; D051379:Mice; D008815:Mice, Inbred Strains; D051437:Renal Insufficiency / Q000517:prevention & control
D019268:Antibodies, Antineutrophil Cytoplasmic; D016207:Cytokines; D000939:Epitopes; D006146:Guanidines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; C037258:gusperimus