Levels of serum chemokines discriminate clinical myelopathy associated with human T lymphotropic virus type 1 (HTLV-1)/tropical spastic paraparesis (HAM/TSP) disease from HTLV-1 carrier state
Levels of serum chemokines discriminate clinical myelopathy associated with human T lymphotropic virus type 1 (HTLV-1)/tropical spastic paraparesis (HAM/TSP) disease from HTLV-1 carrier state
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DOI：
10.1111/j.1365-2249.2006.03150.x
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发表时间：
2006-08-01
影响因子：
4.6
通讯作者：
Carvalho, E. M.
中科院分区：
文献类型：
--
作者：
Guerreiro, J. B.;Santos, S. B.;Carvalho, E. M.
大约5%感染人类T淋巴细胞病毒1型（HTLV-1）的人发展为临床脊髓病或热带痉挛性下肢轻瘫（HAM/TSP），其与高水平的Th 1细胞因子、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α相关。已知趋化因子诱导细胞因子分泌并引导免疫细胞运输至疾病部位。本研究测量了与细胞培养物中自主释放的IFN-γ相关的血清趋化因子。HTLV-1感染通过酶联免疫吸附试验（ELISA）确定，并通过Western blot确认。受试者包括HTLV-1携带者（n = 56）、HAM/TSP患者（n = 31）和健康HTLV-1血清阴性志愿者对照（n = 20）。通过ELISA定量培养物中单核细胞自主释放的血清趋化因子和IFN-γ。与HTLV-1携带者相比，HAM/TSP患者的血清趋化因子显示CXCL 9和CXCL 10水平显著升高，CCL 2水平显著降低，CCL 11和CCL 24的量相似。HAM/TSP患者血清中的CCL 11和CCL 24显著低于对照组。当HAM/TSP和HTLV-1携带者作为组合组时，IFN-γ与CXCL 9和CXCL 10正相关。然而，尽管大部分HTLV-1携带者具有高IFN-γ水平，但这些趋化因子在携带者中并没有增加。本研究表明，体循环中高水平的CXCL 9和CXCL 10以及低血清CCL 2水平是HAM/TSP的特征。HTLV-1感染和Tax和/或其他病毒编码因子介导的病理过程触发T细胞活化与自体IFN-γ释放可能参与调节趋化因子释放。
Approximately 5% of people infected with human T lymphotropic virus type 1 (HTLV-1) develop clinical myelopathy or tropical spastic paraparesis (HAM/TSP) that is associated with high-levels of Th1 cytokines, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Chemokines are known to induce cytokine secretion and direct the trafficking of immune cells to sites of disease. The present study measured serum chemokines correlated with autonomously released IFN-gamma in cell cultures. HTLV-1 infection was defined by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot. Subjects included HTLV-1 carriers (n = 56), patients with HAM/TSP (n = 31) and healthy HTLV-1 seronegative volunteer controls (n = 20). Serum chemokines and IFN-gamma autonomously released by mononuclear cells in culture were quantified by ELISA. Compared to HTLV-1 carriers, serum chemokines in HAM/TSP patients showed significantly increased levels of CXCL9 and CXCL10, significantly diminished levels of CCL2 and similar amounts of CCL11 and CCL24. In contrast, CCL11 and CCL24 were significantly lower in serum of HAM/TSP patients than either control. IFN-gamma was positively correlated with CXCL9 and CXCL10 when HAM/TSP and HTLV-1 carriers were used as a combined group. However, despite a large proportion of HTLV-1 carriers having high IFN-gamma levels, these chemokines were not increased in carriers. This study showed that high levels of CXCL9 and CXCL10 in the systemic circulation and low serum CCL2 levels are features of HAM/TSP. HTLV-1 infection and Tax and/or additional viral encoded factor-mediated pathological processes triggering T cell activation with autogenous IFN-gamma release are probably involved in regulating chemokine release.