503 Intestinal permeability correlates with disease activity and DNA methylation changes in lupus patients

Objective Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease that can involve multiple organ systems. Although the exact cause of SLE is unknown, several studies have suggested that increased intestinal permeability may play a role in the pathogenesis of the disease. The aim of this study was to elucidate the relationship between intestinal permeability and disease activity in lupus patients. Methods A total of 25 female lupus patients were included in this study. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were used as an indicator of disease activity. Plasma zonulin levels were measured, using an ELISA, as a marker of intestinal permeability. In addition, genome-wide DNA methylation patterns were assessed for 19 of the lupus patients using the Infinium MethylationEPIC array. Linear regression and Pearson's correlations were used to evaluate the correlation between zonulin concentrations and SLEDAI scores, as well as the relationship of DNA methylation levels with zonulin concentrations adjusting for age and race. Results Intestinal permeability, as reflected by plasma zonulin levels, was positively correlated with disease activity in SLE patients (p-value = 7.60x10⁻³, r = 0.53). The analysis of DNA methylation levels showed 5 significant CpG sites (FDR-adjusted p-value < 0.05) and 20 suggestive CpG sites (p-value < 1x10⁻⁵) associated with zonulin levels. Among significant associations, the CpG site in the LRIG1 gene (cg14159396, FDR-adjusted p-value = 3.77x10⁻²) suggested progressive demethylation levels with increasing intestinal permeability in lupus patients. Interestingly, the protein encoded by this gene has been proposed to play a role in the control of intestinal epithelium homeostasis. Conclusion Our data suggest a significant correlation between increased intestinal permeability and disease activity in lupus patients. Further, increased intestinal permeability might be associated with epigenetic changes that could play a role in the pathogenesis of SLE.