| Project/Area Number |
11470146
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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 | Kagoshima University |
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Principal Investigator |
OSAME Mitsuhiro Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (10041435)
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| Co-Investigator(Kenkyū-buntansha) |
USUKU Koichiro Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30281223)
NAKAGAWA Masanori Kagoshima University, University Hospital, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 講師 (50198040)
ARIMURA Kimiyoshi Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20159510)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥11,000,000 (Direct Cost: ¥11,000,000)
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| Keywords | HAM occurrence / Analysis of Genetic Factors / Analysis of Viral Factors / ROC curve / Candidate Gene Analysis / Tax subtype / non-HLA factors / Regression Analysis / HAM / HTLV-Iキャリア / HLA classI / HLA classII / プロウイルス量 / 細胞傷害性T細胞 / HTLV-Iプロウイルス量 / PCR定量 / 疾患感受性 / 遺伝子多型 / HLA |
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| Research Abstract |
We have analyzed the genetic and viral background of the pathological mechanism of HTLV-I associated myelopathy HAM and have followed up more than 300 patients of HAM and at least 64 patients more than 10 years.
For genetic background, we have found that HLA-A【thermodynamics】02 and HLA-Cw【thermodynamics】08 have conferred protection to be HAM and HLA-B【thermodynamics】5401 and HLA-DRB1【thermodynamics】0101 predisposition to the disease. To further clarify the relation between HTLV-I proviral load and these factors, we have tried to determine the cut off value that can distinguish the patients with HAM and HTLV-I infected healthy individuals. For this purpose, we have used ROC curve and been able to show that the viral load of 2 % of peripheral blood mononuclear cells is good for differentiate these two groups with more than 80 % specificity and BOX sensitivity. On dividing HAM patient group and carrier group by using this 2 % viral load, we have been able to show the difference of genetic
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background at the different viral load. HLA-A【thermodynamics】02 and HLA-DRB1【thermodynamics】0101 have shown the genetic effect at the low viral load and HLA-B【thermodynamics】5401 at high viral load. This may be due to the different host response at the different environment such as virus effect. From the regression analysis, we have shown that it may be possible to predict HAM or not more than 80 % accuracy in our cohort by using the above mentioned factors.
We have further analyzed non-HLA genetic factors by candidate gene analysis and have been able to find predisposing or protective factors to the disease. THF-a (-863A) allele have shown predisposing effect at-the high viral load, SDF-1-801A 3'UTR have decreased the risk to be HAM and IL-15 191C allele have had effect to decrease the viral load. Including these factors to the regression analysis, we have been able to predict 88 % cases of HAM.
From the viral factor analysis, we have found HTLV-I tax A subtype that had predisposing effect to HAM. Since this tax A subtype prevails more in Caribbean area, this may explain high frequency to be HAM from HTLV-I carriers. We have also analyzed adhesion molecules and found that CD44 splice v6/v10 existed more frequently on the lymphocytes from patients with HAM than carriers. Less
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