Work

Sex-specific transcriptional reprogramming of CD4 + T cells and monocytes in giant cell arteritis reveals female-biased immune dysregulation

Year: 2026

Type: article

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.

Source: RMD Open

DOI: 10.1136/rmdopen-2026-007355