HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) inflammatory network
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) inflammatory network
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DOI：
10.2174/187152808785107642
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发表时间：
2008-06-01
期刊：
影响因子：
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通讯作者：
Carneiro-Proietti, Anna B.
中科院分区：
文献类型：
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作者：
Goncalves, Denise U.;Proietti, Fernando A.;Carneiro-Proietti, Anna B.
HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）是一种全身性免疫介导的炎症性疾病，可损害除神经外的其他组织，主要是眼部、风湿病和皮肤病。超过90%的htlv -1感染者终生无症状，这种逆转录病毒在其CD4+ t淋巴细胞中无限期存在。感染的维持是由于淋巴细胞的增殖，这些淋巴细胞携带一种原病毒并表达HTLV-1蛋白，特别是Tax，促进了受感染T细胞的活性和选择性扩增。高原病毒载量与疾病进展有关，这与宿主与病毒之间的不平衡有关。在无症状携带者和HAM/TSP患者中，细胞毒性T淋巴细胞丰富且慢性活化。无症状携带者具有高频率的促炎单核细胞和抗炎IL-10+CD4+和IL-10+CD8+ t细胞，作为一种免疫调节机制来平衡单核细胞来源的tnf - α。一个假定的免疫调节事件将是控制其整体免疫状态的关键。在HAM/TSP中，促炎微环境是免疫学特征的标志。活化的CD8+ t细胞（HLA-DR+）频率增加，CD18表面高表达已被观察到。在血液和脑脊液中，可以发现1型细胞因子水平升高，如干扰素-(IFN)- γ、肿瘤坏死因子(TNF)- α、白细胞介素(IL)-2和促炎因子IL-6。关于进展，HLA多态性可能影响HAM/TSP，等位基因HLA- a *2与保护有关。作者发现，HAM/TSP与b细胞百分比下降、T/ b细胞比例增加和CD8+ T细胞活化密切相关。这些免疫学参数已被提出作为HAM/TSP的预后生物标志物。
HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a systemic immune-mediated inflammatory disease and tissues other than nervous can be damaged, mainly ocular, rheumatic and dermatologic. Over 90% of HTLV-1-infected individuals remain lifelong asymptomatic and this retrovirus persists indefinitely in their CD4+ T-lymphocytes. The infection is maintained due to the proliferation of lymphocytes that harbor a provirus and express HTLV-1 proteins, particularly Tax, promoting an active and selective expansion of infected T cells. High proviral load is related to disease progression, which is correlated to disequilibrium between host and virus. Cytotoxic T lymphocytes are abundant and chronically activated in asymptomatic carriers and in HAM/TSP patients. The asymptomatic carriers were shown to have a high frequency of pro-inflammatory monocytes and anti-inflammatory IL-10+CD4+ and IL-10+CD8+ T-cells, as an immunoregulatory mechanism to counterbalance the monocyte-derived TNF-alpha. A putative immunomodulatory event would be the key to control their overall immunological status. In HAM/TSP, a pro-inflammatory microenvironment is the hallmark of the immunological profile. Enhanced frequency of activated CD8+ T-cells (HLA-DR+) in combination with high CD18 surface expression has been seen. In blood and cerebrospinal fluid, increased levels of Type-1 cytokines, as interferon-(IFN)-gamma, Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-2, and pro-inflammatory IL-6, can be found. Concerning the progression, HLA polymorphisms may influence HAM/TSP and the allele HLA-A*2 has been associated with protection. The authors showed that HAM/TSP is strongly associated with a decreased percentage of B-cells, with enhanced T/B-cell ratio and activated CD8+ T-cells. These immunological parameters have been proposed as a prognostic biomarker for HAM/TSP.