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

• Published in: Clinical immunology (Orlando, Fla.) Vol. 221; p. 108602
• Main Authors: Perry, Daniel J., Titov, Anton A., Sobel, Eric S., Brusko, Todd M., Morel, Laurence
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2020
• Subjects: Adult; Aged; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Female; Gene Expression; Humans; Immunophenotyping; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Middle Aged; T-Lymphocyte Subsets - immunology; Young Adult
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2020.108602

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). Peripheral blood was analyzed using standardized flow cytometry panels. Transcriptional analysis of CD4+ T cells was performed by microarrays and Nanostring assays. 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. 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. •CD4+ T cells from SLE patients express higher levels of metabolic and immunoregulatory genes.•SLE patients with low disease activity present higher frequencies of activated effector T cells than healthy controls.•Activated T cells defines a group in which African American patients were overrepresented.•A higher expression of immunoregulatory and metabolic genes is associated with activated immunophenotypes in SLE patients.•T cell activation is positively correlated with metabolic gene expression in SLE patients but not in healthy controls.