Bolanos Rachel, Martinez-Maza Otoniel, Zhang Zuo-Feng, Hussain Shehnaz, Sehl Mary, Sinsheimer Janet S, D'Souza Gypsyarn, Jenkins Frank, Wolinsky Steven, Detels Roger
Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA.
Departments of Obstetrics and Gynecology, and Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA.
Cancer Res Front. 2018;4(1):45-59. doi: 10.17980/2018.45.
AIDS-related Kaposi's sarcoma (AIDS-KS) risk remains substantially elevated compared with the general population, even among patients who receive effective combination antiretroviral therapy. This study investigated the role of inflammatory and immune activating biomarkers in AIDS-KS in men who have sex with men in the Multicenter AIDS Cohort study between 1984 and 2010. Concentrations of 24 serum biomarkers; IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, sGP130, sIL-2Rα, sIL-6R, eotaxin, MCP-1, MCP4, MIP 1β, TARC, BLC-BCA1, IP-10, GM-CSF, IFN-γ, BAFF, sCD14, CD27, sTNFR-2, sCRP, and TNF-α were tested longitudinally in 1,501 men. The concentrations of each biomarker were compared between AIDS-KS cases and controls at multiple time points, 0-1 years, 1-2 years, 2-3 year, 3-5 years and over 5 years, prior to KS diagnosis or study termination, using univariate non-parametric Kruskal-Wallis tests and logistic regression, adjusted for HBV and HCV co-infection, race/ethnicity, age at last visit, education, smoking and CD4+ cell count. In univariate analyses, concentrations of four markers were consistently higher in cases; sIL-2Rα, IP-10, sTNFR-2, MCP-1, and five were higher in controls; GM-CSF, IL-6, MIP-1β, sCRP, sGP130. In the adjusted models concentrations of four markers were significantly inversely associated with AIDS-KS risk including sGP130 (OR=0.14, 95% CI = 0.03-0.73, BAFF (OR=0.60, 95% CI =0.16-0.90), sCRP (OR=0.61, 95% CI = 0.43-0.87) and IL-6 (OR=0.51, 95% CI = 0.35-0.76). These results support a role for markers of immune activation and inflammation in AIDS-KS and may highlight pathways to be targeted for risk stratification or therapeutics.
与普通人群相比,艾滋病相关的卡波西肉瘤(AIDS-KS)风险仍然显著升高,即使在接受有效联合抗逆转录病毒治疗的患者中也是如此。本研究在1984年至2010年的多中心艾滋病队列研究中,调查了炎症和免疫激活生物标志物在与男性发生性关系的男性的AIDS-KS中的作用。检测了24种血清生物标志物的浓度;白细胞介素-1β(IL-1β)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)、白细胞介素-12p70、可溶性糖蛋白130(sGP130)、可溶性白细胞介素-2受体α(sIL-2Rα)、可溶性白细胞介素-6受体(sIL-6R)、嗜酸性粒细胞趋化因子、单核细胞趋化蛋白-1(MCP-1)、单核细胞趋化蛋白4(MCP4)、巨噬细胞炎症蛋白1β(MIP 1β)、胸腺和活化调节趋化因子(TARC)、B淋巴细胞趋化因子(BLC-BCA1)、干扰素诱导蛋白10(IP-10)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、干扰素-γ(IFN-γ)、B细胞活化因子(BAFF)、可溶性CD14(sCD14)、CD27、可溶性肿瘤坏死因子受体2(sTNFR-2)、可溶性C反应蛋白(sCRP)和肿瘤坏死因子-α(TNF-α),对1501名男性进行了纵向检测。在KS诊断或研究终止前,使用单变量非参数克鲁斯卡尔-沃利斯检验和逻辑回归,在多个时间点(0至1年、1至2年、2至3年、3至5年和5年以上)比较了AIDS-KS病例和对照之间每种生物标志物的浓度,并对乙肝病毒和丙肝病毒合并感染、种族/民族、最后一次就诊时的年龄、教育程度、吸烟情况和CD4 +细胞计数进行了调整。在单变量分析中,病例组中四种标志物的浓度始终较高;sIL-2Rα、IP-10、sTNFR-2、MCP-1,对照组中有五种较高;GM-CSF、IL-6、MIP-1β、sCRP、sGP130。在调整模型中,四种标志物的浓度与AIDS-KS风险显著负相关,包括sGP130(比值比[OR]=0.14,95%置信区间[CI]=0.03 - 0.73)、BAFF(OR=0.60,95% CI =0.16 - 0.90)、sCRP(OR=0.61,95% CI = 0.43 - 0.87)和IL-6(OR=0.51,95% CI = 0.35 - 0.76)。这些结果支持免疫激活和炎症标志物在AIDS-KS中的作用,并可能突出了可用于风险分层或治疗的靶向途径。