Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection.
Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection.
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氧化的脂蛋白与HIV-1感染中炎症和免疫激活的标记有关。
DOI：
10.1097/qad.0000000000001238
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发表时间：
2016-11-13
期刊：
影响因子：
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通讯作者：
Currier JS
中科院分区：
文献类型：
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作者：
Kelesidis T;Jackson N;McComsey GA;Wang X;Elashoff D;Dube MP;Brown TT;Yang OO;Stein JH;Currier JS
慢性HIV-1感染中免疫功能障碍的发病机制尚不清楚，氧化脂质的潜在作用已被提出。我们假设氧化的低密度和高密度脂蛋白（HDLox，LDLox）有助于HIV-1相关的免疫功能障碍。在艾滋病临床试验组（ACTG）A5260中，234名HIV感染的抗逆转录病毒治疗（ART）初治受试者随机接受替诺福韦-恩曲他滨联合蛋白酶抑制剂或雷特格韦治疗，到第24周及以后HIV-1 RNA <50拷贝/ml。采用斯皮尔曼（偏）相关分析法评估了入组时和ART后（第96周）炎症标志物（IL-6、hs-CRP、D-二聚体）、免疫活化标志物（sCD 163、sCD 14、sIL-2 r、CD 38、HLA-DR）、炎性单核细胞标志物（CD 14 + CD 16+）、T细胞衰老标志物（CD 28、CD 57）和耗竭标志物（PD 1）与HDLox、LDLox之间的相关性。在96周的ART治疗中，HDLox下降，LDLox增加。在基线和随着时间的推移，HDLox（但LDLox不一致）与大多数炎症和免疫激活标志物（但不包括衰老/衰竭）之间观察到正相关，即使在调整多重比较、人口统计学、入门CD 4计数和HIV-1 RNA后也是如此。在所有时间点，HDLox与IL-6（r=0.19-0.29，p<0.01）和sCD 163（r=0.14-0.41 p≤0.04）呈正相关。这些前瞻性纵向数据表明，氧化脂蛋白可能有助于ART的持续免疫激活。
The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized low- and high-density lipoproteins (HDLox, LDLox) contribute to HIV-1 related immune dysfunction. In the AIDS Clinical Trials Group (ACTG) A5260, 234 HIV-infected antiretroviral therapy (ART)-naïve participants were randomized to receive tenofovir-emtricitabine plus protease inhibitors or raltegravir and had HIV-1 RNA <50 copies/ml by week 24 and thereafter. Associations between biomarkers of inflammation (IL-6, hs-CRP, D-Dimer), immune activation (sCD163, sCD14, sIL-2r, CD38, HLA-DR), inflammatory monocytes (CD14+CD16+), T cell senescence (CD28, CD57) and exhaustion (PD1) and HDLox, LDLox were assessed at entry and after ART (week 96) with Spearman (partial) correlations. HDLox declined and LDLox increased over 96 weeks of ART. Positive associations were observed at baseline and over time between HDLox, (but not consistently for LDLox) and most markers of inflammation and immune activation (but not senescence/exhaustion), even after adjustment for multiple comparisons, demographics, entry CD4 count and HIV-1 RNA. HDLox was positively associated with IL-6 (r=0.19–0.29, p<0.01), and sCD163 (r=0.14–0.41 p≤0.04) at all timepoints. These prospective longitudinal data suggest that oxidized lipoproteins may contribute to persistent immune activation on ART.