Daniel J Perry1, Anton A Titov1, Eric S Sobel2, Todd M Brusko3, Laurence Morel4. 1. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA. 2. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL, USA. 3. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA; Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA. 4. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL, USA. Electronic address: morel@ufl.edu.
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.
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:SLECD4+ T cells showed an increased expression of oxidative phosphorylation and immunoregulatory genes. SLEpatients presented higher frequencies of activated CD38+HLA-DR+ T cells than HC. Hierarchical clustering identified a group of SLEpatients 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 SLEpatients 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.
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