Immunophenotyping reveals distinct subgroups of lupus patients based on their activated T cell subsets

Objective: This study performed an integrated analysis of the cellular and transcriptional differences in peripheral immune cells between patients with Systemic Lupus Erythematosus (SLE) and healthy controls (HC). Methods: Peripheral blood was analyzed using standardized flow cytometry panels. Transcriptional analysis of CD4⁺ T cells was performed by microarrays and Nanostring assays. Results: SLE CD4⁺ T cells showed an increased expression of oxidative phosphorylation and immunoregulatory genes. SLE patients presented higher frequencies of activated CD38⁺HLA-DR⁺ T cells than HC. Hierarchical clustering identified a group of SLE patients among which African Americans were overrepresented, with highly activated T cells, and higher frequencies of Th1, Tfh, and plasmablast cells. T cell activation was positively correlated with metabolic gene expression in SLE patients but not in HC. Conclusions: SLE subjects presenting with activated T cells and a hyperactive metabolic signature may represent an opportunity to correct aberrant immune activation through targeted metabolic inhibitors.