围生期感染 HIV-1 的儿童中出现的一过性病毒反弹会引起独特的可溶性免疫代谢特征，与 CD4/CD8 比值降低有关。
Transient Viral Rebound in Children with Perinatally Acquired HIV-1 Induces a Unique Soluble Immunometabolic Signature Associated with Decreased CD4/CD8 Ratio.
机构信息
Molecular Immunology Laboratory, Hospital General Universitario Gregorio Marañón, Health Research Institute Gregorio Marañón (IiSGM), Madrid, Spain.
Universitat Rovira i Virgili, Tarragona, Spain.
出版信息
J Pediatric Infect Dis Soc. 2023 Apr 18;12(3):143-151. doi: 10.1093/jpids/piad008.
BACKGROUND
To determine by multi-omic analysis changes in metabolites, lipids, and proteins as a consequence of transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV).
METHODS
Plasma samples from children with PHIV and with tVR (first episode of transient RNA-HIV viral load >20 copies/ml followed by suppression) on the time-point immediately before (pre-tVR) and after (post-tVR) the tVR were assessed. Multi-omic analyses were performed using nLC-Orbitrap, GC-qTOF-MS, and LC-qTOF-MS.
RESULTS
Comparing pre- and post-tVR time-points, HIV-1 children with tVR (n = 5) showed a trend to a decrease in ratio CD4/CD8 (p = 0.08) but no significant differences were observed in plasma metabolites, lipids, or proteins. Post-tVR condition was compared with a reference group of children with PHIV with persistent viral control (n = 9), paired by sex, age, and time under antiretroviral treatment. A total of 10 proteins, 8 metabolites, and 2 lipids showed significant differences (p < 0.05): serotransferrin, clusterin, kininogen-1, succinic acid, threonine, 2-hydroxyisovaleric acid, methionine, 2-hydroxyglutaric, triacylglyceride 50:0 (TG50:0), and diacylglyceride 34:1 (DG34:1) were upregulated while alpha-2-macroglobulin, apolipoprotein A-II, carboxylic ester hydrolase, apolipoprotein D, coagulation factor IX, peptidase inhibitor 16, SAA2-SAA4 readthrough, oleic acid, palmitoleic acid, and D-sucrose downregulated on post-tVR time-point compared to the reference group. Ratio CD4/CD8 correlated with apolipoprotein A-II, DG34:1, and methionine (p = 0.004; ρ = 0.71, p = 0.016; ρ = -0.63; and p = 0.032; ρ = -0.57, respectively). Nadir CD4+ correlated inversely with kininogen-1 (p = 0.022; ρ = -0.60) and positively with D-sucrose (p = 0.001; ρ = 0.77).
CONCLUSIONS
tVR followed by suppression implies changes in soluble proteins, lipids, and metabolites that correlate with immunological parameters, mainly ratio CD4/CD8, that decreased after tVR. These distinct soluble biomarkers could be considered potential biomarkers of immune progression.
背景
通过对代谢物、脂质和蛋白质的多组学分析，确定儿童感染人类免疫缺陷病毒 1 （PHIV）后，病毒短暂反弹（tVR）导致的变化。
方法
对 PHIV 儿童在 tVR 前（pre-tVR）和 tVR 后（post-tVR）的即刻时间点的血浆样本进行分析。使用 nLC-Orbitrap、GC-qTOF-MS 和 LC-qTOF-MS 进行多组学分析。
结果
比较 pre-tVR 和 post-tVR 时间点，tVR（n=5）的 HIV-1 儿童 CD4/CD8 比值呈下降趋势（p=0.08），但血浆代谢物、脂质或蛋白质无明显差异。将 post-tVR 组与 PHIV 儿童的持续病毒控制参考组（n=9）进行配对，配对因素为性别、年龄和抗逆转录病毒治疗时间。共有 10 种蛋白质、8 种代谢物和 2 种脂质表现出显著差异（p<0.05）：转铁蛋白、载脂蛋白 A-II、凝血因子 IX、凝血酶原抑制剂 16、SAA2-SAA4 通读、α-2-巨球蛋白、载脂蛋白 D、角蛋白 1、簇蛋白、激肽原-1、琥珀酸、苏氨酸、2-羟异戊酸、甲硫氨酸、2-羟戊二酸、三酰甘油 50:0（TG50:0）和二酰甘油 34:1（DG34:1）上调，而载脂蛋白 A-II、DG34:1、甲硫氨酸下调apolipoprotein A-II、apolipoprotein D、carboxylic ester hydrolase、coagulation factor IX、peptidase inhibitor 16、SAA2-SAA4 readthrough、oleic acid、palmitoleic acid 和 D-蔗糖与参考组相比，在 post-tVR 时间点。CD4/CD8 比值与载脂蛋白 A-II、DG34:1 和甲硫氨酸呈正相关（p=0.004；ρ=0.71，p=0.016；ρ=-0.63；p=0.032；ρ=-0.57）。最低 CD4+与激肽原-1 呈负相关（p=0.022；ρ=-0.60），与 D-蔗糖呈正相关（p=0.001；ρ=0.77）。
结论
tVR 后抑制意味着可溶性蛋白质、脂质和代谢物发生变化，这些变化与免疫参数相关，主要是 CD4/CD8 比值，在 tVR 后下降。这些不同的可溶性生物标志物可被视为免疫进展的潜在生物标志物。
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