1998 Fiscal Year Final Research Report Summary
Epitope analysis of myeloperoxdase-specific anti-neutrophil
| Project/Area Number |
08670265
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
SUZUKI Kazuo NIID,Bioactive Molecules, Chief of Lab., 生物活性物質部・生体防御物質室, 室長 (20192130)
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| Co-Investigator(Kenkyū-buntansha) |
OKAWARA Akiko NIID,Bioactive Molecules, Research Ass., 生物活性物質部, 研究員 (30260277)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Autoimmune diseases / Autoantibody / MPO-ANCA / Neutrophils / Vasculitis / Glomerulonephritis / Myeloperoxidase / Epitope analysis |
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| Research Abstract |
Autoantibody, myeloperoxidase-specific anti-neutrophul cytoplasmic antibody (MPO-ANCA) has been detected in vasculitis. However, it appears that the titer of MPO-ANCA does not always reflect the activity of the disease. This apparent inconsistency may be mainly attributed to different epitope recognition by MPO-ANCA among sera of the patients. Epitope analysis of MPO-ANCA may explain the correlation between the disease activity and the production of MPO-ANCA.Moreover, mouse anti-MPO antibody induces superoxide production of neutrophils activated with TNFC? though FcRII.These observations suggest that MPO-ANCA recognizes MPO molecule on the surface of patients, neutrophils with specific epitope and stimulates them though FcRII.In order to understand the activation of neutrophils of the patients related with severity of the diseases, epitope of MPO-ANCA should be analyzed. Epitope mapping of autoantibodies using recombinant fragments have been established as a panel for examining reactivity with sera from patients of MPO-ANCA-related diseases. Epitope analysis of sera of patients with MPO-ANCA-related renal diseases and vasculitis was conducted by Western blotting and ELISA using a panel set of recombinant deletion mutants of MPO.Most of the sera reacted with either of the region of N- or C- terminus of the heavy chain, whereas no serum reacted with the light chain regions. The reactivity to the specific sites decreased in the serv of patients with pulmonary fibrosis, alveolar hemorrhage and rapidly progressive glomerulonephritis. Moreover, the epitope profiles showing the oligo-clonality were classified to two and four groups. The profiles had relation with clinical features of the diseases. When score was estimated by the classification of epitope, it was related with the severity of these clinical features. Further, we analyzed the epitopes of MPO-ANCA of patients with Kawasaki Disease.
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[Publications] Asagoe, K., Yamamoto, K., Takahashi, A., Suzuki, K., Maeda, A., Nohgawa, M., Harakawa, N., Takano, K., Mukaida, N., Masushima, K., Okuma, M., and Sasada, M.: "Down-regulation of CXCR2 expression on human polymorphonuclear leukocytes by TNF-alpha" J.Immunol.160. 4518-4525 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Tomizawa, K., Mine, E., Fujii, A., Y.Ohashi, Y., Yamagoe, S., Ishida-Okawara, A., Y.Hashimoto, Ito, M., Tanokura, M., Yamamoto, T., Arimura, Y., Nagasawa, T., Mizuno, S.and Suzuki, K.: "A panel set for epitope analysis of myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody MPO-ANCA using recombinant hexamer histidine-tagged MPO Deletion Mutants" J Clin.Immunol.18. 142-152 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Minoshima, S., Arimura, Y., Nakabayashi, K., Kitamoto, K., Nagasawa, T., Ishida-Okawara, A.and Suzuki, K.: "Increased release of myelopreoxidase in vitro from neutrophils of patients with myelopreoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis." Nephrology. 3. 527-534 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Otani, I., Ishida-Okawara, A., Yamagoe, S., Miyoshi-Koshio, T., Arimura, Y., Nagasawa, T., Mizuno, S.and Suzuki, K.: "Myelopreoxidase (MPO) fragments reacting with a serum of patient with MPO-ANCA positive glomerulonephritis." J.Infection and Chemother. 3. 164-169 (1997)
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「研究成果報告書概要(欧文)」より
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