Global DNA methylation profiling of CD4+ T cells from patients with systemic lupus erythematosus

ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic-relapsing autoimmune disease of incompletely understood etiology. Recent evidence strongly supports an epigenetic contribution to the pathogenesis of lupus. To understand the extent and nature of dysregulated DNA methylation in lupus T cells, we performed a genome-wide DNA methylation study in CD4+ T cells from 12 lupus patients and 12 normal healthy controls. Cytosine methylation was quantified in 27,578 CG pairs located within the promoter regions of 14,495 genes. We identified 236 hypomethylated and 105 hypermethylated CG sites in lupus CD4+ T cells compared to normal controls, consistent with a global hypomethylation in lupus T cells. Further analysis identified hypomethylation in genes involved in connective tissue development including CD9, MMP9, and PDGFRA. Hypermethylated genes highlight “response to nutrients” ontology such as folate biosynthesis, suggesting a link between environmental factor and lupus and emphasizing the role of folate in DNA methylation. In addition, the transcription factor RUNX3 was hypermethylated in lupus CD4+ T cells. Protein-protein interaction maps identified a transcription factor, HNF4a, as a regulatory hub affecting a number of differentially methylated genes. Functional annotations such as apoptosis is also overrepresented. Further, our data indicate that the methylation status of certain genes predicts disease activity in lupus patients. This work provides a foundation to begin identifying novel pathogenic pathways in lupus T cells and developing novel epigenetic biomarkers for disease activity in lupus. We employed microarray-based technologies to perform a genome-wide DNA methylation assay and quantify CD4+ T cell DNA methylation levels at 27,578 CG sites spanning 14,495 genes of 11 lupus patients and 12 healthy controls.

ORGANISM(S): Homo sapiens

SUBMITTER: Mikhail Dozmorov 

PROVIDER: E-GEOD-27895 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress