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HIV/AIDS免疫无应答者肺脾气虚证的蛋白质组学研究及生物标志物鉴定

Proteomic investigation and biomarker identification of lung and spleen deficiency syndrome in HIV/AIDS immunological nonresponders.

作者信息

Wang Yi-Ting, Ji Shao-Xiu, Xia Xin-Yi, Wan Ting-Jun, Zou Jia-Xi, Li Bai-Xue, Hu Qian-Nan, Chen Xin, Mu Jie, Feng Quan-Sheng, Wen Li

机构信息

College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

College of Basic Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

J Thorac Dis. 2023 Mar 31;15(3):1460-1472. doi: 10.21037/jtd-23-322. Epub 2023 Mar 29.

DOI:10.21037/jtd-23-322
PMID:37065569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10089843/
Abstract

BACKGROUND

Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) immunological nonresponders (HIV/AIDS-INRs) whose CD4 cell counts do not rebound after highly active antiretroviral therapy (HAART) treatment usually experience severely impaired immune function and high mortality. Traditional Chinese medicine (TCM) has many advantages in the field of AIDS, especially its promotion of patients' immune reconstitution. Accurate differentiation of TCM syndromes is a prerequisite for guiding an effective TCM prescription. However, the objective and biological evidence for identification of the TCM syndromes in HIV/AIDS-INRs remains lacking. Lung and spleen deficiency (LSD) syndrome, a typical HIV/AIDS-INR syndrome, was examined on in this study.

METHODS

We first performed a proteomic study of LSD syndrome in INRs (INRs-LSD) using tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS) and screened them against the healthy and undocumented identifiable groups. The TCM syndrome-specific proteins were subsequently validated based on bioinformatics analysis and enzyme-linked immunosorbent assay (ELISA).

RESULTS

A total of 22 differentially expressed proteins (DEPs) were screened in INRs-LSD compared to the healthy group. Based on bioinformatic analysis, these DEPs were found to be mainly associated with the immunoglobin A (IgA)-generated intestinal immune network. In addition, we examined the TCM syndrome-specific proteins alpha-2-macroglobulin (A2M) and human selectin L (SELL) with ELISA and found that they were both upregulated, which was consistent with the proteomic screening results.

CONCLUSIONS

A2M and SELL were finally identified as potential biomarkers for INRs-LSD, providing a scientific and biological basis for identifying typical TCM syndromes in HIV/AIDS-INRs and an opportunity to build a more effective TCM treatment system for HIV/AIDS-INRs.

摘要

背景

人类免疫缺陷病毒(HIV)和获得性免疫缺陷综合征(AIDS)免疫无应答者(HIV/AIDS-INRs)在接受高效抗逆转录病毒治疗(HAART)后,其CD4细胞计数未出现反弹,通常会经历严重受损的免疫功能和高死亡率。中医在艾滋病领域具有诸多优势,尤其是在促进患者免疫重建方面。准确辨别中医证候是指导有效中医处方的前提。然而,目前仍缺乏用于识别HIV/AIDS-INRs中医证候的客观生物学证据。本研究对肺脾气虚证这一典型的HIV/AIDS-INR证候进行了研究。

方法

我们首先使用串联质谱标签结合液相色谱-串联质谱法(TMT-LC-MS/MS)对免疫无应答者肺脾气虚证(INRs-LSD)进行了蛋白质组学研究,并将其与健康组和未记录的可识别组进行筛选对比。随后基于生物信息学分析和酶联免疫吸附测定(ELISA)对中医证候特异性蛋白进行了验证。

结果

与健康组相比,在INRs-LSD中总共筛选出22种差异表达蛋白(DEPs)。基于生物信息学分析,发现这些DEPs主要与免疫球蛋白A(IgA)产生的肠道免疫网络相关。此外,我们用ELISA检测了中医证候特异性蛋白α-2-巨球蛋白(A2M)和人选择素L(SELL),发现它们均上调,这与蛋白质组学筛选结果一致。

结论

最终确定A2M和SELL为INRs-LSD的潜在生物标志物,为识别HIV/AIDS-INRs中的典型中医证候提供了科学和生物学依据,并为建立更有效的HIV/AIDS-INRs中医治疗体系提供了契机。

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