Department of Obstetrics and Gynecology, AIDS Institute, UCLA David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA.
Infections and Cancer Epidemiology, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
J Acquir Immune Defic Syndr. 2019 Mar 1;80(3):e53-e63. doi: 10.1097/QAI.0000000000001916.
HIV infection is associated with increased susceptibility to common pathogens, which may trigger chronic antigenic stimulation and hyperactivation of B cells, events known to precede the development of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL).
To explore whether cumulative exposure to infectious agents contributes to AIDS-NHL risk, we tested sera from 199 AIDS-NHL patients (pre-NHL, average lead time 3.9 years) and 199 matched HIV-infected controls from the Multicenter AIDS Cohort Study, for anti-IgG responses to 18 pathogens using multiplex serology. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression models.
We found no association between cumulative exposure to infectious agents and AIDS-NHL risk (OR 1.01, 95% CI: 0.91 to 1.12). However, seropositivity for trichodysplasia spinulosa polyomavirus (TSPyV), defined as presence of antibodies to TSPyV capsid protein VP1, was significantly associated with a 1.6-fold increase in AIDS-NHL risk (OR 1.62, 95% CI: 1.02 to 2.57). High Epstein-Barr virus (EBV) anti-VCA p18 antibody levels closer to the time of AIDS-NHL diagnosis (<4 years) were associated with a 2.6-fold increase in AIDS-NHL risk (OR 2.59, 95% CI: 1.17 to 5.74). In addition, high EBV anti-EBNA-1 and anti-ZEBRA antibody levels were associated with 2.1-fold (OR 0.47, 95% CI: 0.26 to 0.85) and 1.6-fold (OR 0.57, 95% CI: 0.35 to 0.93) decreased risk of AIDS-NHL, respectively.
Our results do not support the hypothesis that cumulative exposure to infectious agents contributes to AIDS-NHL development. However, the observed associations with respect to TSPyV seropositivity and EBV antigen antibody levels offer additional insights into the pathogenesis of AIDS-NHL.
HIV 感染会增加对常见病原体的易感性，这可能会引发慢性抗原刺激和 B 细胞的过度激活，这些事件被认为先于 AIDS 相关非霍奇金淋巴瘤（AIDS-NHL）的发展。
为了探讨累积暴露于传染性病原体是否有助于 AIDS-NHL 的发病风险，我们使用多重血清学方法检测了来自 Multicenter AIDS Cohort Study 的 199 例 AIDS-NHL 患者（pre-NHL，平均潜伏期 3.9 年）和 199 例匹配的 HIV 感染对照者的血清中针对 18 种病原体的抗-IgG 反应。使用条件逻辑回归模型估计比值比（OR）和 95％置信区间（CI）。
我们没有发现累积暴露于传染性病原体与 AIDS-NHL 发病风险之间存在关联（OR 1.01，95％CI：0.91 至 1.12）。然而，血清学阳性的 Trichodysplasia spinulosa polyomavirus（TSPyV），定义为存在针对 TSPyV 衣壳蛋白 VP1 的抗体，与 AIDS-NHL 风险增加 1.6 倍相关（OR 1.62，95％CI：1.02 至 2.57）。在 AIDS-NHL 诊断时（<4 年）更接近 EBV 抗-VCA p18 抗体水平较高，与 AIDS-NHL 发病风险增加 2.6 倍相关（OR 2.59，95％CI：1.17 至 5.74）。此外，高 EBV 抗-EBNA-1 和抗-ZEBRA 抗体水平分别与 AIDS-NHL 的发病风险降低 2.1 倍（OR 0.47，95％CI：0.26 至 0.85）和 1.6 倍（OR 0.57，95％CI：0.35 至 0.93）相关。
我们的结果不支持累积暴露于传染性病原体有助于 AIDS-NHL 发展的假设。然而，与 TSPyV 血清阳性和 EBV 抗原抗体水平相关的观察结果为 AIDS-NHL 的发病机制提供了更多的见解。
