Page 127 - ITPS-7-3

INNOSC Theranostics

and Pharmacological Sciences

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 Chen 1,2,3 *

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

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
*Corresponding author:
Youdinghuan Chen conditions and ultimate death if left untreated. Although much is known about the
(y.david.chen@ncis.org) role of CD4T-mediated immunity, the understanding of CD4T-related transcriptomic
Citation: Chen Y. Transcriptomic patterns remains incomplete. This proof-of-concept study aims to identify a
signature of CD4-expressing T-cell transcriptome-wide gene signature for CD4T abundance by Least Absolute Shrinkage
abundance developed in healthy and Selection Operator (LASSO) regression modeling in 340 healthy peripheral blood
peripheral blood predicts strong
anti-retroviral therapeutic response samples. The optimized LASSO model demonstrated computational robustness
in HIV-1: A retrospective and (tenfold average Pearson’s r = 0.89) and biological relevance evidenced by four
proof-of-concept study. INNOSC significant Gene Ontology terms (all odds ratio [OR] ≥ 4.5 and false discovery rate
Theranostics and Pharmacological
Sciences. 2024;7(3):2761. ≤0.05). Subsequently, in an independent cohort with 24 HIV-1-infected men who
doi: 10.36922/itps.2761 received anti-retroviral therapies, there is a significant, positive association between
Received: January 17, 2024 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,
Accepted: May 16, 2024 the gene expression pattern associated with CD4T abundance is predictable,
Published Online: July 12, 2024 generalizable, and biologically relevant, shedding new light on the importance of
Copyright: © 2024 This CD4T abundance.
is an Open-Access article
distributed under the terms
of the Creative Commons Keywords: CD4T; Gene signature; HIV-1; Immune cells; Transcriptomics
AttributionNoncommercial License,
permitting all non-commercial use,
distribution, and reproduction in any
medium, provided the original work
is properly cited. 1. Introduction
Publisher’s Note: AccScience CD4-expressing T lymphocytes (CD4Ts) are crucial players in the human immune
Publishing remains neutral with system. The CD4T plays a role in the modulation of antiviral immune responses
regard to jurisdictional claims in
published maps and institutional primarily by enhancing the function of other immune cells. During the initial stages
affiliations

Volume 7 Issue 3 (2024) 1 doi: 10.36922/itps.2761