2006 Fiscal Year Final Research Report Summary
Clinical Investigation for Virus-Host Interactions and its Implication in the Development of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP).
| Project/Area Number |
17590886
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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 |
Neurology
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| Research Institution | Kanazawa Medical University (2006)
Kagoshima University (2005) |
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Principal Investigator |
SAITO Mineki Kanazawa Medical University, Associate Professor, 医学部, 助教授 (40398285)
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| Co-Investigator(Kenkyū-buntansha) |
FURUKAWA Yoshitaka Kagoshima University, Hospital, Lecturer, 医学部歯学部附属病院, 講師 (00359978)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Virus / Neurological disease / Human Genetics / Immunology / Clinical |
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| Research Abstract |
Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is observed only in 1-2% of HTLV-1 infected individuals. We have previously reported that HTLV-1 Tax subtype, several HLA and non-HLA genes are closely associated with the development of HAM/TSP. Based on these findings, we developed the best-fit logistic regression equation to predict the odds of HAM/TSP. We applied this equation to 181 consecutively ascertained healthy HTLV-1 carriers (HCs) and found a significant association between a high odds of HAM/TSP and two factors: brisk patellar deep tendon reflexes, which suggest latent central nervous system compromise, and flower cell (ATL cell)-like abnormal lymphocytes. Our data suggests the usefulness of our equation for detecting subclinical HAM/TSP-related neurological abnormalities. We further analyzed CD4+ and CD8+ T cells in PBMCs from HAM/TSP patients, HCs and normal uninfected controls by flow cytometry based analyses. We have used synthetic tetramers composed of HLA and its immunodominant epitope peptide to analyze Env-specific CD4+ T and Tax-specific CD8+ T cells directly from peripheral blood. Significantly higher frequency of activated and clonally expanded tetramer+CD4+ and tetramer+CD8+ T cells were observed in HAM/TSP patients than HCs, suggesting that active and continus expansion of HTLV-1 specific T cells during chronic infection play a role in the development of HAM/TSP.
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Research Products
(13 results)
