Viremic and Virologically Suppressed HIV Infection Increases Age-Related Changes to Monocyte Activation Equivalent to 12 and 4 Years of Aging, Respectively
Viremic and Virologically Suppressed HIV Infection Increases Age-Related Changes to Monocyte Activation Equivalent to 12 and 4 Years of Aging, Respectively
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DOI：
10.1097/qai.0000000000000559
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发表时间：
2015-05-01
影响因子：
3.6
通讯作者：
Jaworowski, Anthony
中科院分区：
文献类型：
--
作者：
Angelovich, Thomas A.;Hearps, Anna C.;Jaworowski, Anthony
背景：HIV感染和正常衰老均存在慢性炎症和免疫激活，并与炎症性疾病相关。然而，HIV对年龄相关的先天性免疫变化的影响程度以及最能反映这些变化的生物标志物仍不清楚。方法和结果：我们测量了309名个体的已建立的天然免疫衰老生物标志物，其中包括88名病毒学抑制(VS)和52名病毒学(病毒载量分别为每毫升50拷贝)HIV阳性个体。在HIV阳性个体中，单核细胞活化的可溶性(即CXCL10、可溶性CD163、新喋呤)和细胞生物标志物(即炎性CD16(+)单核细胞的比例)水平增加，并且仅被病毒抑制部分改善。病毒携带者和VS HIV阳性者的年龄相关单核细胞激活生物标志物的水平分别与12岁和4岁的未感染对照组相似。病毒型HIV感染与某些单核细胞激活标志物(如新喋呤)随年龄的变化速度加快有关，而在VS患者中，随后与年龄相关的变化发生的速度与对照组相似，尽管绝对水平更高。我们进一步将CXCL10确定为单核细胞激活的一个强大的可溶性生物标记物，强调了这种趋化因子作为预后标记物的潜在效用。意义：这些发现可能部分解释了艾滋病毒阳性个体中炎症性年龄相关疾病的增加，并潜在地表明了这些疾病背后的病理机制，尽管病毒受到抑制，这些疾病仍然存在。
Background: Chronic inflammation and immune activation occur in both HIV infection and normal aging and are associated with inflammatory disease. However, the degree to which HIV influences age-related innate immune changes, and the biomarkers which best reflect them, remains unclear.Methods and Results: We measured established innate immune aging biomarkers in 309 individuals including 88 virologically suppressed (VS) and 52 viremic (viral load 50 copies per milliliter, respectively) HIV-positive individuals. Levels of soluble (ie, CXCL10, soluble CD163, neopterin) and cellular (ie, proportions of inflammatory CD16(+) monocytes) biomarkers of monocyte activation were increased in HIV-positive individuals and were only partially ameliorated by viral suppression. Viremic and VS HIV-positive individuals show levels of age-related monocyte activation biomarkers that are similar to uninfected controls aged 12 and 4 years older, respectively. Viremic HIV infection was associated with an accelerated rate of change of some monocyte activation markers (eg, neopterin) with age, whereas in VS individuals, subsequent age-related changes occurred at a similar rate as in controls, albeit at a higher absolute level. We further identified CXCL10 as a robust soluble biomarker of monocyte activation, highlighting the potential utility of this chemokine as a prognostic marker.Implications: These findings may partially explain the increased prevalence of inflammatory age-related diseases in HIV-positive individuals and potentially indicate the pathological mechanisms underlying these diseases, which persist despite viral suppression.