Sex-specific transcriptional reprogramming of CD4+ T cells and monocytes in giant cell arteritis reveals female-biased immune dysregulation
- 1Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clinic, Universitat de Barcelona, Institut D`Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- 2Institute of Parasitology and Biomedicine López-Neyra (IPBLN), Spanish National Research Council (CSIC), Granada, Spain
- 3Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain
Abstract
Objective Giant cell arteritis (GCA) is a systemic vasculitis associated with severe ischaemic complications. Despite recognised sex differences in disease susceptibility and clinical presentation, the molecular mechanisms underlying these variations remain unclear.Methods We performed a transcriptome-wide association study to identify sex-associated transcriptional profiles in CD14+ monocytes and CD4+ T cells from 18 treatment-naive patients with GCA and 31 controls.Results Differential expression revealed marked transcriptional alterations in female patients with GCA compared with healthy women, particularly in CD4+ T cells, whereas no differentially expressed genes (DEGs) were identified in male patients compared with healthy men. Most DEGs also significantly differed between female and male patients. Specifically, CD4+ T cells of female patients showed transcriptional reprogramming characterised by upregulation of genes involved in vascular interaction and tissue homing (FLT1, NOTCH1, FURIN, CLDN5 and MYL9) and downregulation of cytotoxic/Th1 effector-related genes (TBX21, EOMES, CX3CR1, KLRF1, CCL5 and CCL4), consistent with enhanced vascular engagement and redistribution of effector programmes. Monocytes from female patients showed differential expression of key genes, including downregulation of NR4A1, a regulator of differentiation of vascular surveillance monocytes, and upregulation of ADAMTS2, involved in extracellular matrix remodelling.Conclusion These findings reveal sex-specific transcriptional landscapes in GCA, with female patients exhibiting CD4+ T cell reprogramming towards vascular engagement and dysregulation of monocyte genes with vascular relevance. These sex-dimorphic signatures provide a mechanistic basis for sex differences in GCA and highlight the value of sex-stratified approaches for improved patient management.
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BibTeX
@article{espigolfrigole2026sexspecific,
title = {{Sex-specific transcriptional reprogramming of CD4+ T cells and monocytes in giant cell arteritis reveals female-biased immune dysregulation}},
author = {Georgína Espigol-Frigolé and Javier Martin and Laura Ciudad and Esteban Ballestar and Maria C. Cid and Sergio Prieto-González and José Hernández-Rodríguez and Lourdes Ortiz-Fernández and Ana Márquez and Elkyn Estupiñán-Moreno and Valeria Serrano-García and Gonzalo Borrego-Yaniz and Raúl Burgos-Morata},
journal = {RMD Open},
year = {2026},
month = nov,
doi = {10.1136/rmdopen-2026-007355},
url = {https://doi.org/10.1136/rmdopen-2026-007355},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sex-specific transcriptional reprogramming of CD4+ T cells and monocytes in giant cell arteritis reveals female-biased immune dysregulation
AU - Georgína Espigol-Frigolé
AU - Javier Martin
AU - Laura Ciudad
AU - Esteban Ballestar
AU - Maria C. Cid
AU - Sergio Prieto-González
AU - José Hernández-Rodríguez
AU - Lourdes Ortiz-Fernández
AU - Ana Márquez
AU - Elkyn Estupiñán-Moreno
AU - Valeria Serrano-García
AU - Gonzalo Borrego-Yaniz
AU - Raúl Burgos-Morata
PY - 2026
DA - 2026/11/08
JO - RMD Open
DO - 10.1136/rmdopen-2026-007355
UR - https://doi.org/10.1136/rmdopen-2026-007355
AB - Objective Giant cell arteritis (GCA) is a systemic vasculitis associated with severe ischaemic complications. Despite recognised sex differences in disease susceptibility and clinical presentation, the molecular mechanisms underlying these variations remain unclear.Methods We performed a transcriptome-wide association study to identify sex-associated transcriptional profiles in CD14+ monocytes and CD4+ T cells from 18 treatment-naive patients with GCA and 31 controls.Results Differential expression revealed marked transcriptional alterations in female patients with GCA compared with healthy women, particularly in CD4+ T cells, whereas no differentially expressed genes (DEGs) were identified in male patients compared with healthy men. Most DEGs also significantly differed between female and male patients. Specifically, CD4+ T cells of female patients showed transcriptional reprogramming characterised by upregulation of genes involved in vascular interaction and tissue homing (FLT1, NOTCH1, FURIN, CLDN5 and MYL9) and downregulation of cytotoxic/Th1 effector-related genes (TBX21, EOMES, CX3CR1, KLRF1, CCL5 and CCL4), consistent with enhanced vascular engagement and redistribution of effector programmes. Monocytes from female patients showed differential expression of key genes, including downregulation of NR4A1, a regulator of differentiation of vascular surveillance monocytes, and upregulation of ADAMTS2, involved in extracellular matrix remodelling.Conclusion These findings reveal sex-specific transcriptional landscapes in GCA, with female patients exhibiting CD4+ T cell reprogramming towards vascular engagement and dysregulation of monocyte genes with vascular relevance. These sex-dimorphic signatures provide a mechanistic basis for sex differences in GCA and highlight the value of sex-stratified approaches for improved patient management.
SN - 2056-5933
ER -