Birmann Brenda M, Breen Elizabeth C, Stuver Sherri, Cranston Beverly, Martínez-Maza Otoniel, Falk Kerstin I, Okayama Akihiko, Hanchard Barrie, Mueller Nancy, Hisada Michie
Department of Epidemiology, Brigham and Women's Hospital and Harvard School of Public Health, Boston, MA 02115, USA.
Int J Cancer. 2009 Feb 1;124(3):614-21. doi: 10.1002/ijc.24012.
The natural history of human T-lymphotropic virus type I (HTLV-I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV-I-endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)-i.e., 51 HTLV-I-positive ("carriers") and 51 HTLV-I-negative individuals ("noncarriers") from each population-by age, sex and blood collection year. We compared plasma concentrations of markers of T-cell-mediated (antigen-specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV-I noncarriers, Japanese noncarriers had higher covariate-adjusted mean levels of T-cell activation markers, including antibody to Epstein-Barr virus nuclear antigen-1 (reciprocal titer 27 vs. 71, respectively, p=0.005), soluble interleukin-2 receptor-alpha (477 vs. 623 pg/mL, p=0.0008) and soluble CD30 (34 vs. 46 U/mL, p=0.0001) and lower levels of C-reactive protein (1.1 vs. 0.43 microg/mL, p=0.0004). HTLV-I infection was associated with activated T-cell immunity in Jamaicans but with diminished T-cell immunity in Japanese persons. The observed population differences in background and HTLV-I-related host immunity correspond closely to the divergent natural histories of infection observed among HTLV-I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk.
人类嗜T淋巴细胞病毒I型(HTLV-I)的自然史已显示因地理区域不同而有显著差异。这些差异包括成人T细胞淋巴瘤(ATL)和HTLV-I相关脊髓病/热带痉挛性截瘫(HAM/TSP)风险的对比模式,这可能部分归因于宿主对感染的免疫反应差异。为了描述不同人群中宿主免疫的变化,我们比较了日本和牙买加HTLV-I流行人群的血清学免疫标志物模式。我们将来自宫崎队列研究(日本)和食品处理人员研究(牙买加)的204名有存档血液的参与者进行匹配,即每个群体中51名HTLV-I阳性(“携带者”)和51名HTLV-I阴性个体(“非携带者”),匹配因素为年龄、性别和采血年份。我们使用回归模型和相关系数比较了T细胞介导的(抗原特异性)和非特异性免疫标志物的血浆浓度。与牙买加HTLV-I非携带者相比,日本非携带者的T细胞活化标志物的协变量调整后平均水平更高,包括抗EB病毒核抗原-1抗体(倒数滴度分别为27和71,p=0.005)、可溶性白细胞介素-2受体α(477对623 pg/mL,p=0.0008)和可溶性CD30(34对46 U/mL,p=0.0001),而C反应蛋白水平更低(1.1对0.43 microg/mL,p=0.0004)。HTLV-I感染在牙买加人与活化的T细胞免疫相关,但在日本人中与T细胞免疫减弱相关。观察到的不同人群在背景和HTLV-I相关宿主免疫方面的差异与在日本和牙买加的HTLV-I携带者中观察到的不同感染自然史密切对应,并证实了宿主免疫状态在ATL和HAM/TSP风险对比模式中的作用。