INTRACELLULAR T-CELL METABOLOMICS REVEALS DISTINCT SIGNATURES ACROSS HUMAN T-LYMPHOTROPIC VIRUS TYPE 1 CLINICAL PHENOTYPES AND UNINFECTED CONTROLS
- 1Universidade Municipal de São Caetano do Sul (USCS), São Caetano do Sul, SP, Brazil
- 2University of Bristol, United Kingdom
- 3Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil
Abstract
Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated with heterogeneous clinical outcomes, ranging from persistent asymptomatic infection to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Aim: This study investigated phenotype-associated intracellular metabolic differences in isolated CD4+ T cells across these clinical groups. Methodology: The cross-sectional analytical cohort comprised 44 participants: 15 asymptomatic HTLV-1 carriers, 12 patients with HAM/TSP, 7 patients with ATLL, and 10 uninfected controls. CD4+ T cells were isolated from cryopreserved peripheral blood mononuclear cells by immunomagnetic negative selection. Intracellular metabolites were analyzed using high-resolution mass spectrometry. Analytical features were evaluated using Kruskal-Wallis screening followed by Dunn’s post hoc testing with contrast-specific Benjamini-Hochberg false-discovery rate correction. Results: The largest curated differential feature set was observed between ATLL and asymptomatic carriers, comprising 348 putatively annotated MSI level 2 features, followed by HAM/TSP versus asymptomatic carriers with 190 features and ATLL versus uninfected controls with 163 features. Lipid-related features, particularly glycerophospholipids, sphingolipids, and oxidized glycerophospholipids, were prominently represented. A total of 155 features were shared between the ATLL-versus-asymptomatic-carrier and HAM/TSP-versus-asymptomatic-carrier comparisons, all with concordant directionality. Discussion: Intracellular CD4+ T-cell metabolomics revealed both shared metabolic alterations and phenotype-specific signatures associated with distinct clinical outcomes of HTLV-1 infection. The predominant metabolic changes involved lipid remodeling, particularly glycerophospholipids and sphingolipids, suggesting a shared metabolic background across symptomatic HTLV-1 disease with superimposed mechanisms related to chronic inflammation in HAM/TSP and malignant transformation in ATLL. Conclusion: These findings indicate that intracellular CD4+ T-cell metabolomic profiling captures biological heterogeneity across the clinical spectrum of HTLV-1 infection and provides a framework for future biomarker discovery and mechanistic studies. Validation in larger cohorts and functional investigations will be necessary to confirm these observations.
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BibTeX
@article{mateos2026intracellular,
title = {{INTRACELLULAR T-CELL METABOLOMICS REVEALS DISTINCT SIGNATURES ACROSS HUMAN T-LYMPHOTROPIC VIRUS TYPE 1 CLINICAL PHENOTYPES AND UNINFECTED CONTROLS}},
author = {Sheila De Oliveira Garcia MATEOS and Marcos Eduardo Souza ABREU and Felipe Custódio Carvalho DOS SANTOS and Rubens De Assis Santos SEBASTIÃO and Guilherme Lucchesi D'angelo BRAZ and Sofia Luari Moelas GIUZIO and Fábio Eudes LEAL and Luiza Amoroso LAMBAZ and Lara GALLUCCI and Cadiele Oliana REICHERTV and Luís Alberto de Pádua Covas LAGE and Juliana PEREIRA and Hebert CULLER and Youko NUKUI and Ester Cerdeira SABINO and Iart Luca SHYTAJ and Álex Aparecido Rosini SILVA},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.106792},
url = {https://doi.org/10.1016/j.htct.2026.106792},
note = {CC BY},
}
RIS
TY - JOUR
TI - INTRACELLULAR T-CELL METABOLOMICS REVEALS DISTINCT SIGNATURES ACROSS HUMAN T-LYMPHOTROPIC VIRUS TYPE 1 CLINICAL PHENOTYPES AND UNINFECTED CONTROLS
AU - Sheila De Oliveira Garcia MATEOS
AU - Marcos Eduardo Souza ABREU
AU - Felipe Custódio Carvalho DOS SANTOS
AU - Rubens De Assis Santos SEBASTIÃO
AU - Guilherme Lucchesi D'angelo BRAZ
AU - Sofia Luari Moelas GIUZIO
AU - Fábio Eudes LEAL
AU - Luiza Amoroso LAMBAZ
AU - Lara GALLUCCI
AU - Cadiele Oliana REICHERTV
AU - Luís Alberto de Pádua Covas LAGE
AU - Juliana PEREIRA
AU - Hebert CULLER
AU - Youko NUKUI
AU - Ester Cerdeira SABINO
AU - Iart Luca SHYTAJ
AU - Álex Aparecido Rosini SILVA
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.106792
UR - https://doi.org/10.1016/j.htct.2026.106792
AB - Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated with heterogeneous clinical outcomes, ranging from persistent asymptomatic infection to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Aim: This study investigated phenotype-associated intracellular metabolic differences in isolated CD4+ T cells across these clinical groups. Methodology: The cross-sectional analytical cohort comprised 44 participants: 15 asymptomatic HTLV-1 carriers, 12 patients with HAM/TSP, 7 patients with ATLL, and 10 uninfected controls. CD4+ T cells were isolated from cryopreserved peripheral blood mononuclear cells by immunomagnetic negative selection. Intracellular metabolites were analyzed using high-resolution mass spectrometry. Analytical features were evaluated using Kruskal-Wallis screening followed by Dunn’s post hoc testing with contrast-specific Benjamini-Hochberg false-discovery rate correction. Results: The largest curated differential feature set was observed between ATLL and asymptomatic carriers, comprising 348 putatively annotated MSI level 2 features, followed by HAM/TSP versus asymptomatic carriers with 190 features and ATLL versus uninfected controls with 163 features. Lipid-related features, particularly glycerophospholipids, sphingolipids, and oxidized glycerophospholipids, were prominently represented. A total of 155 features were shared between the ATLL-versus-asymptomatic-carrier and HAM/TSP-versus-asymptomatic-carrier comparisons, all with concordant directionality. Discussion: Intracellular CD4+ T-cell metabolomics revealed both shared metabolic alterations and phenotype-specific signatures associated with distinct clinical outcomes of HTLV-1 infection. The predominant metabolic changes involved lipid remodeling, particularly glycerophospholipids and sphingolipids, suggesting a shared metabolic background across symptomatic HTLV-1 disease with superimposed mechanisms related to chronic inflammation in HAM/TSP and malignant transformation in ATLL. Conclusion: These findings indicate that intracellular CD4+ T-cell metabolomic profiling captures biological heterogeneity across the clinical spectrum of HTLV-1 infection and provides a framework for future biomarker discovery and mechanistic studies. Validation in larger cohorts and functional investigations will be necessary to confirm these observations.
SN - 2531-1379
SN - 2531-1387
ER -