Clinical Investigation for Virus-Host Interactions and its Implication in the Development of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP).

病毒-宿​​主相互作用的临床研究及其对 HTLV-1 相关脊髓病/热带痉挛性截瘫 (HAM/TSP) 发展的影响。

• 批准号: 17590886
• 负责人: SAITO Mineki
• 金额: $ 2.24万
• 依托单位: Kanazawa Medical University (2006)Kagoshima University (2005)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590886/
• 关键词: Virus; Neurological disease; Human Genetics; Immunology; Clinical

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.

人类t细胞嗜淋巴病毒1型（HTLV-1）相关脊髓病/热带痉挛性麻痹（HAM/TSP）仅在HTLV-1感染个体的1-2%中观察到。我们之前报道HTLV-1 Tax亚型、几种HLA和非HLA基因与HAM/TSP的发生密切相关。基于这些发现，我们开发了最佳拟合逻辑回归方程来预测HAM/TSP的几率。我们将该方程应用于181名连续确定的健康HTLV-1携带者（hc），发现HAM/TSP的高几率与两个因素之间存在显著关联：活跃的髌骨深腱反射，这表明中枢神经系统存在潜在的损害，以及花细胞（ATL细胞）样异常淋巴细胞。我们的数据表明我们的方程对于检测亚临床HAM/ tsp相关的神经异常是有用的。我们进一步通过流式细胞术分析了HAM/TSP患者、hc和正常未感染对照的pbmc中的CD4+和CD8+ T细胞。我们使用由HLA及其免疫优势表位肽组成的合成四聚体直接从外周血中分析env特异性CD4+ T和tax特异性CD8+ T细胞。HAM/TSP患者中激活和克隆扩增的四聚体+CD4+和四聚体+CD8+ T细胞的频率明显高于hcc，提示慢性感染期间HTLV-1特异性T细胞的活跃和持续扩增在HAM/TSP的发展中起作用。

项目成果

HTLV-Iと疾患(分担) HAM/TSPの免疫遺伝学

HTLV-I与疾病（分享）HAM/TSP的免疫遗传学

• 发表时间: 2007
• 作者: Tsumoto K;Ejima A;Senczuk M;Kita Y;Arakawa T.;齊藤峰輝
• 通讯作者: 齊藤峰輝

Genetic variability in the extracellular matrix protein as a determinant of risk for developing HTLV-I-associated neurological disease.

细胞外基质蛋白的遗传变异是发生 HTLV-I 相关神经系统疾病风险的决定因素。

• 发表时间: 2006
• 期刊: Immunogenetics. 57(12)
• 作者: Nobuhara Y;et al.
• 通讯作者: et al.

Abnormalities of spinal MRIs implicate clinical variability in HTLV-I-associated myelopathy.

脊髓 MRI 的异常表明 HTLV-I 相关脊髓病的临床变异。

• 发表时间: 2007
• 期刊: Journal of Neurovirology (印刷中)
• 作者: Shiraishi H;et al.;Yano T et al.;Umehara F
• 通讯作者: Umehara F

Geographical distribution and disease associations of the CD45 exon 6 138G variant.

CD45 外显子 6 138G 变体的地理分布和疾病关联。

• 发表时间: 2006
• 期刊: Immunogenetics 58 (2-3)
• 作者: Fujio Umehara;Kenichi Mishima;Nobuaki Egashira;Ayumi Ogata;Katsunori Iwasaki;Michihiro Fujiwara.;Ward V
• 通讯作者: Ward V

Flow cytometry evaluation of the T-cell receptor Vβ repertoire among human T-cell lymphotropic virus type-1 (HTLV-1) infected individuals : Effect of interferon alpha therapy in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

流式细胞术评估人 T 细胞嗜淋巴细胞病毒 1 型 (HTLV-1) 感染个体中 T 细胞受体 Vβ 库：干扰素 α 治疗对 HTLV-1 相关脊髓病/热带痉挛性截瘫 (HAM/TSP) 的影响

• 发表时间: 2006
• 期刊: Journal of the Neurological Sciences 246(1-2)
• 作者: Saito;M;et al.
• 通讯作者: et al.