Rachel Bolanos, Otoniel Martinez-Maza, Zuo-Feng Zhang, Shehnaz Hussain, Mary Sehl, Janet S Sinsheimer, Gypsyarn D'Souza, Frank Jenkins, Steven Wolinsky, Roger Detels
{"title":"血清炎症生物标志物sGP130、IL-6、sCRP和BAFF水平的降低与男男性行为者患艾滋病相关卡波西肉瘤的可能性增加有关。","authors":"Rachel Bolanos, Otoniel Martinez-Maza, Zuo-Feng Zhang, Shehnaz Hussain, Mary Sehl, Janet S Sinsheimer, Gypsyarn D'Souza, Frank Jenkins, Steven Wolinsky, Roger Detels","doi":"10.17980/2018.45","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":87228,"journal":{"name":"Cancer research frontiers","volume":"4 1","pages":"45-59"},"PeriodicalIF":0.0000,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845762/pdf/","citationCount":"4","resultStr":"{\"title\":\"Decreased levels of the serum inflammatory biomarkers, sGP130, IL-6, sCRP and BAFF, are associated with increased likelihood of AIDS related Kaposi's sarcoma in men who have sex with men.\",\"authors\":\"Rachel Bolanos, Otoniel Martinez-Maza, Zuo-Feng Zhang, Shehnaz Hussain, Mary Sehl, Janet S Sinsheimer, Gypsyarn D'Souza, Frank Jenkins, Steven Wolinsky, Roger Detels\",\"doi\":\"10.17980/2018.45\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":87228,\"journal\":{\"name\":\"Cancer research frontiers\",\"volume\":\"4 1\",\"pages\":\"45-59\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2018-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845762/pdf/\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer research frontiers\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.17980/2018.45\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer research frontiers","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.17980/2018.45","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 4
摘要
与一般人群相比,艾滋病相关的卡波西肉瘤(AIDS-KS)的风险仍然显著升高,即使在接受有效的抗逆转录病毒联合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男男性行为者艾滋病- ks中的作用。24种血清生物标志物浓度;对1501名男性进行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和TNF-α的纵向检测。使用单变量非参数Kruskal-Wallis检验和logistic回归,比较在KS诊断或研究终止前0-1年、1-2年、2-3年、3-5年和5年以上的多个时间点AIDS-KS病例和对照组的每种生物标志物的浓度,调整HBV和HCV合并感染、种族/民族、最后一次就诊年龄、教育程度、吸烟和CD4+细胞计数。在单变量分析中,病例中四种标记物的浓度始终较高;对照组sIL-2Rα、IP-10、sTNFR-2、MCP-1和5较高;GM-CSF, IL-6, MIP-1β, sCRP, sGP130。在调整后的模型中,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)和IL-6 (OR=0.51, 95% CI = 0.35-0.76)四种标志物的浓度与AIDS-KS风险呈显著负相关。这些结果支持免疫激活和炎症标志物在艾滋病- ks中的作用,并可能突出危险分层或治疗的靶向途径。
Decreased levels of the serum inflammatory biomarkers, sGP130, IL-6, sCRP and BAFF, are associated with increased likelihood of AIDS related Kaposi's sarcoma in men who have sex with men.
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.