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秘鲁与1型人类嗜T淋巴细胞病毒(HTLV-1)相关脊髓病/热带痉挛性截瘫(HAM/TSP)相关的前病毒载量和免疫标志物

Proviral load and immune markers associated with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Peru.

作者信息

Best I, Adaui V, Verdonck K, González E, Tipismana M, Clark D, Gotuzzo E, Vanham G

机构信息

Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.

出版信息

Clin Exp Immunol. 2006 Nov;146(2):226-33. doi: 10.1111/j.1365-2249.2006.03208.x.

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) is the aetiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study is to identify which ex vivo and in vivo markers are associated independently with HAM/TSP in a Peruvian population. Eighty-one subjects (33 men/48 women) were enrolled: 35 presented with HAM/TSP, 33 were asymptomatic HTLV-1 carriers (ACs) and 13 were HTLV-1-seronegative controls (SCs). Ex vivo markers included T cell proliferation and Th1 [interferon (IFN)-gamma], Th2 [interleukin (IL)-4, IL-5], proinflammatory [tumour necrosis factor (TNF)-alpha] and anti-inflammatory (IL-10) cytokine production in non-stimulated peripheral blood mononuclear cell (PBMC) cultures. In vivo CD4(+) T cell count, markers of Th1 [interferon-inducible protein (IP)-10] and Th2 (sCD30) activity in plasma and HTLV-1 proviral load in PBMCs were also evaluated. In univariate analysis, several markers, including T cell proliferation, IFN-gamma, IP-10, sCD30 and proviral load were associated with HAM/TSP, but in a multiple logistic regression analysis only the proviral load remained associated significantly with disease manifestation [adjusted OR 9.10 (1.24-66.91)]. Our findings suggest that HAM/TSP is associated primarily with proviral load, whereas the observed association with some immune markers seems secondary.

摘要

人类嗜T淋巴细胞病毒1型(HTLV-1)是HTLV-1相关脊髓病/热带痉挛性截瘫(HAM/TSP)的病原体。本研究的目的是确定在秘鲁人群中,哪些体外和体内标志物与HAM/TSP独立相关。共纳入81名受试者(33名男性/48名女性):35例患有HAM/TSP,33例为无症状HTLV-1携带者(ACs),13例为HTLV-1血清阴性对照者(SCs)。体外标志物包括未刺激的外周血单核细胞(PBMC)培养物中的T细胞增殖以及Th1[干扰素(IFN)-γ]、Th2[白细胞介素(IL)-4、IL-5]、促炎[肿瘤坏死因子(TNF)-α]和抗炎(IL-10)细胞因子产生。还评估了体内CD4(+)T细胞计数、血浆中Th1[干扰素诱导蛋白(IP)-10]和Th2(可溶性CD30)活性标志物以及PBMC中的HTLV-1前病毒载量。在单变量分析中,包括T细胞增殖、IFN-γ、IP-10、可溶性CD30和前病毒载量在内的几种标志物与HAM/TSP相关,但在多因素逻辑回归分析中,只有前病毒载量仍与疾病表现显著相关[校正比值比9.10(1.24-66.91)]。我们的研究结果表明,HAM/TSP主要与前病毒载量相关,而观察到的与某些免疫标志物的关联似乎是次要的。

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