Inflammatory expression profiles in monocyte-to-macrophage differentiation in patients with systemic lupus erythematosus and relationship with atherosclerosis |
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| Authors: | Benjamin D Korman Chiang-Ching Huang Carly Skamra Peggy Wu Renee Koessler David Yao Qi Quan Huang William Pearce Kim Sutton-Tyrrell George Kondos Daniel Edmundowicz Richard Pope Rosalind Ramsey-Goldman |
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| Institution: | 1.Northwestern University Feinberg School of Medicine, 240 E Huron Street, McGaw M-230, Chicago, IL 60611, USA;2.University of Pittsburgh, 132 Parran Hall, Pittsburgh, PA 15261, USA;3.University of Illinois at Chicago, 840 S. Wood St., (MC 715), Chicago, IL 60612, USA;4.Temple University, 610 University Services Bldg.1601 N. Broad St. Philadelphia, Philadelphia, PA 19122, USA |
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| Abstract: | IntroductionOur objectives were to examine mononuclear cell gene expression profiles in patients with systemic lupus erythematosus (SLE) and healthy controls and to compare subsets with and without atherosclerosis to determine which genes’ expression is related to atherosclerosis in SLE.MethodsMonocytes were obtained from 20 patients with SLE and 16 healthy controls and were in vitro-differentiated into macrophages. Subjects also underwent laboratory and imaging studies to evaluate for subclinical atherosclerosis. Whole-genome RNA expression microarray was performed, and gene expression was examined.ResultsGene expression profiling was used to identify gene signatures that differentiated patients from controls and individuals with and without atherosclerosis. In monocytes, 9 out of 20 patients with SLE had an interferon-inducible signature compared with 2 out of 16 controls. By looking at gene expression during monocyte-to-macrophage differentiation, we identified pathways which were differentially regulated between SLE and controls and identified signatures based on relevant intracellular signaling molecules which could differentiate SLE patients with atherosclerosis from controls. Among patients with SLE, we used a previously defined 344-gene atherosclerosis signature in monocyte-to-macrophage differentiation to identify patient subgroups with and without atherosclerosis. Interestingly, this signature further classified patients on the basis of the presence of SLE disease activity and cardiovascular risk factors.ConclusionsMany genes were differentially regulated during monocyte-to-macrophage differentiation in SLE patients compared with controls. The expression of these genes in mononuclear cells is important in the pathogenesis of SLE, and molecular profiling using gene expression can help stratify SLE patients who may be at risk for development of atherosclerosis. |
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