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

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

doi:10.21037/jtd-23-322

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

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

Authors

Yi-Ting Wang¹, Shao-Xiu Ji¹, Xin-Yi Xia², Ting-Jun Wan¹, Jia-Xi Zou¹, Bai-Xue Li¹, Qian-Nan Hu¹, Xin Chen¹, Jie Mu¹, Quan-Sheng Feng¹, Li Wen¹

Affiliations

¹ College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
² College of Basic Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

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.

Keywords: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS); biomarker; immunological nonresponders (INRs); lung and spleen deficiency syndrome; proteomics.