Epigenetic reprogramming in naïve CD4+ T cells favoring T cell activation and Th2 differentiation as an early event in lupus flares

Systemic lupus erythematosus is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus, however, early T cell events triggering disease flares are incompletely understood. We studied DNA methylation in naïve CD4+ T cells from lupus patients to determine if epigenetic landscape change in CD4+ T cells is an early event in lupus flares. A total of 74 lupus patients with disease activity ranging from 0-18 as measured by the systemic lupus erythematosus disease activity index (SLEDAI) were included in this study. Naïve CD4+ T cells were isolated from peripheral blood samples and DNA extracted for genome-wide methylation assessment. RNA was also extracted from a subset of patients to determine the relationship between epigenetic changes and transcriptional activity using RNA sequencing.