HAMの臨床病態・発症機序の解明並びに新治療法の開発に関する研究

我们分析了HTLV-I相关性脊髓病HAM病理机制的遗传和病毒背景，并随访了300多例HAM患者和至少64例患者超过10年。在遗传背景方面，我们发现HLA-A【热力学】02和HLA-Cw【热力学】08对HAM具有保护作用，HLA-B【热力学】5401和HLA-DRB1【热力学】0101易患该疾病。为了进一步明确HTLV-I前病毒载量与这些因素之间的关系，我们试图确定能够区分HAM患者与HTLV-I感染健康人的切值。为此，我们使用了ROC曲线，结果表明外周血单个核细胞的病毒载量为2%对两组的区分有良好的效果，特异性和BOX敏感性均在80%以上。在用2%的病毒载量划分HAM患者组和携带者组时，我们已经能够显示出不同病毒载量下的遗传差异。HLA-A【热力学】02和HLA-DRB1【热力学】0101在低病毒载量下表现出遗传效应，HLA-B【热力学】5401在高病毒载量下表现出遗传效应。这可能是由于宿主在不同环境下的反应不同，如病毒效应。从回归分析中，我们已经表明，在我们的队列中，使用上述因素预测HAM或不超过80%的准确率是可能的。我们通过候选基因分析进一步分析了非hla遗传因素，并能够找到疾病的易感或保护因素。THF-a （-863A）等位基因对高病毒载量有易感作用，SDF-1-801A 3'UTR有降低HAM发病风险的作用，il - 15191c等位基因有降低病毒载量的作用。将这些因素纳入回归分析，我们能够预测88%的HAM病例。从病毒因子分析中，我们发现HTLV-I tax A亚型对HAM有易感作用。由于这种税A亚型在加勒比地区更为普遍，这可能解释了高频是HTLV-I携带者的HAM。我们还分析了粘附分子，发现CD44剪接v6/v10在HAM患者淋巴细胞上的存在频率高于携带者。少

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 … More 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