title: Reduction of MPO-ANCA epitopes in SCG/Kj mice by 15-deoxyspergualin treatment restricted by IgG2b associated with crescentic glomerulonephritis.
abstract: 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.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Nagao
authors.forename: Reina
authors.initials: R
authors.lastname: Kusunoki
authors.forename: Kan
authors.initials: K
authors.lastname: Saiga
authors.forename: Masamichi
authors.initials: M
authors.lastname: Oshima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Tanokura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki
mesh_terms: 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
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D016207:Cytokines; D000939:Epitopes; D006146:Guanidines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; C037258:gusperimus