| Project/Area Number |
15390271
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
ITOYAMA Yasuto TOHOKU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (30136428)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIHARA Kazuo TOHOKU UNIVERSITY, HOSPITAL, ASSOCIATE PROFESSOR, 病院・助教授 (70280873)
NAKASHIMA Ichiro TOHOKU UNIVERSITY, HOSPITAL, RESEARCH ASSOCIATE, 病院・助手 (50333810)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2003: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | multiple sclerosis / demyelinating disease / optic-spinal MS / conventional MS / oligoconal band / cerebral white matter lesions / Th1 / Th2 balance |
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| Research Abstract |
Multiple sclerosis (MS) is classified into two subtypes, 1)conventional MS (CMS) in which demyelinating lesions are disseminated in the central nervous system and 2)optic-spinal MS (OSMS) characterized by the selective involvement of the optic nerves and spinal cord. We investigated clinical and molecular immunological pathogeneses of these two subtypes in Japan.
1.The percentages of MS subtypes in our 120 cases were as follows, CMS (60.8%), OSMS(22.5%), spinal MS(7.5%), secondary progressive MS(5.0%), and primary progressive MS(4.1%). In contrast to CMS, none of OSMS was progressive.
2.The CCR5+CD4+cell subset% and IgG1% in the cerebrospinal fluid (CSF) were significantly lower in OSMS than in CMS, suggesting less Th1 immunity in OSMS.
3.Pathological features of OSMS distinct from CMS were severe tissue destruction, marked macrophage infiltration, and deposition of immunoglobulins and activated complements in the blood vessels.
4.The most characteristic lesions in oligoclonal bands-positive CMS were the periventricular lesions.
5.Phage display analysis of CSF IgG in CMS showed that the sequences highly homologous to herpes viruses were commonly detected as the peptides bound to the patients'IgG.
6.CDR3 spectratyping analysis in MS revealed a frequent expansion of Vβ5.2+T cell clones suggesting the importance of the T cells in the pathogenesis of MS.
7.Indirect immunofluorescence method with patients' sera and mouse brain tissue demonstrated a unique staining pattern specifically seen in OSMS and its high-risk group. The serum autoantibody was named NMO-IgG, and it was shown to bind to CNS microvessels, pia, subpial tissue and Virchow-Robin space. Further studies are needed to analyze NMO-IgG7s useful for early diagnosis of OSMS and its role in the pathogenesis.
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