Lemma Mahlet, Petkov Stefan, Bekele Yonas, Petros Beyene, Howe Rawleigh, Chiodi Francesca
Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.
Armauer Hansen Research Institute, P.O. Box 1005, Addis Ababa, Ethiopia.
Proteomes. 2020 Sep 7;8(3):24. doi: 10.3390/proteomes8030024.
Treatment of HIV-1-infected patients results in improved clinical and immunological conditions, but severe non-AIDS-related conditions still persist. Novel proteomic platforms have identified inflammatory proteins where abundance is dysregulated in adult treated patients, whereas limited data are available in treated HIV-1 infection of children. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we analyzed specimens from 43 vertically HIV-1-infected children receiving antiretroviral treatment (ART) and matched controls in Ethiopia. The infected children were analyzed as a group and separately, according to age of treatment initiation. Proteins displaying a significantly different abundance between groups were hierarchically clustered and presented in heat maps. Random forest analysis was performed to pin-point proteins discriminating between groups; five proteins (STAMBP, CD5, TFG-α, TRANCE, AXIN1) were the strongest prediction factors for treated HIV-1 infection. TRANCE was previously linked to reduced bone mass levels in HIV-1-infected children. CCL4 chemokine, ligand to HIV-1 co-receptor CCR5, was the most critical protein for successful classification between children who initiated ART at different time points. Our data provide evidence that a dysregulated expression of proteins linked to immunological abnormalities and bone metabolism can be found in HIV-1-infected children with prolonged exposure to ART.
对HIV-1感染患者的治疗可改善临床和免疫状况，但严重的非艾滋病相关病症仍然存在。新型蛋白质组学平台已鉴定出在接受治疗的成年患者中丰度失调的炎症蛋白，而关于儿童HIV-1感染治疗的数据有限。我们采用包含92种炎症相关分子的蛋白质组血浆分析方法，对埃塞俄比亚43名接受抗逆转录病毒治疗（ART）的垂直HIV-1感染儿童及其匹配对照的样本进行了分析。将感染儿童作为一个整体进行分析，并根据开始治疗的年龄分别进行分析。对组间丰度有显著差异的蛋白质进行层次聚类，并以热图形式呈现。进行随机森林分析以确定区分不同组的蛋白质；五种蛋白质（STAMBP、CD5、TFG-α、TRANCE、AXIN1）是治疗HIV-1感染的最强预测因子。TRANCE此前与HIV-1感染儿童的骨量水平降低有关。CCL4趋化因子是HIV-1共受体CCR5的配体，是在不同时间点开始接受ART治疗的儿童之间成功分类的最关键蛋白质。我们的数据提供了证据，表明在长期接受ART治疗的HIV-1感染儿童中，可发现与免疫异常和骨代谢相关的蛋白质表达失调。
