AccScience Publishing / ITPS / Volume 7 / Issue 3 / DOI: 10.36922/itps.2761
SHORT COMMUNICATION

Transcriptomic signature of CD4-expressing T-cell abundance developed in healthy peripheral blood predicts strong anti-retroviral therapeutic response in HIV-1: A retrospective and proof-of-concept study

Youdinghuan Chen1,2,3*
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1 National Coalition of Independent Scholars (NCIS), Battleboro, Vermont, United States of America
2 Faculty of Biological and Environmental Informatics, Wilmington University, New Castle, Delaware, United States of America
3 Department of Science, Mathematics, and Biotechnology, University of California-Berkeley Extension, Berkeley, California, United States of America
INNOSC Theranostics and Pharmacological Sciences 2024, 7(3), 2761 https://doi.org/10.36922/itps.2761
Submitted: 17 January 2024 | Accepted: 16 May 2024 | Published: 12 July 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

CD4-expressing T-cells (CD4Ts) play a crucial role in maintaining the normal functioning of the mammalian immune system and overall systemic health. Diseased individuals, such as those infected with the human immunodeficiency virus type I (HIV-1), experience progressive and eventual depletion of CD4T leading to uncurable conditions and ultimate death if left untreated. Although much is known about the role of CD4T-mediated immunity, the understanding of CD4T-related transcriptomic patterns remains incomplete. This proof-of-concept study aims to identify a transcriptome-wide gene signature for CD4T abundance by Least Absolute Shrinkage and Selection Operator (LASSO) regression modeling in 340 healthy peripheral blood samples. The optimized LASSO model demonstrated computational robustness (tenfold average Pearson’s r = 0.89) and biological relevance evidenced by four significant Gene Ontology terms (all odds ratio [OR] ≥ 4.5 and false discovery rate ≤0.05). Subsequently, in an independent cohort with 24 HIV-1-infected men who received anti-retroviral therapies, there is a significant, positive association between the gene signature and a strong anti-retroviral response before (OR = 13.6, P < 0.05) and after adjusting for subject age, sex, and race (OR = 14.4, P < 0.05). Taken together, the gene expression pattern associated with CD4T abundance is predictable, generalizable, and biologically relevant, shedding new light on the importance of CD4T abundance.

Keywords
CD4T
Gene signature
HIV-1
Immune cells
Transcriptomics
Funding
None.
Conflict of interest
The author declares no competing interests.
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing