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

ABSTRACT

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.