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The pathogenesis of Behçet's disease (BD), an inflammatory disease with multisystem involvement, remains poorly understood. This study was undertaken to investigate whether there are DNA methylation abnormalities in BD that might contribute to the pathogenesis of the disease.We examined genome-wide DNA methylation patterns in monocytes and CD4+ T cells from 16 male patients with untreated BD and age, sex, and ethnicity-matched healthy controls. Additional samples were collected from 12 of the same BD patients after treatment and achievement of disease remission. Genome-wide DNA methylation patterns were assessed using the Infinium HumanMethylation450 BeadChip array, which includes485,000 individual methylation sites across the genome.We identified 383 CpG sites in monocytes, and 125 in CD4+ T cells, that were differentially methylated between BD patients and controls. Bioinformatic analysis revealed a pattern of aberrant DNA methylation among genes that regulate cytoskeletal dynamics, suggesting that aberrant DNA methylation of multiple classes of structural and regulatory proteins of the cytoskeleton might contribute to the pathogenesis of BD. Further, treatment of BD modified the differences in DNA methylation observed in patients compared to controls; indeed, among CpG sites that were differentially methylated after disease remission versus before treatment, there was widespread reversal of the direction of aberrant DNA methylation observed between the patient and control groups.The results of this epigenome-wide study-the first such study in BD-provide strong evidence that epigenetic modification of cytoskeletal dynamics underlies the pathogenesis of BD and its response to treatment.

Objectives: Activated innate immunity is implicated in the pathogenesis of Behcet’s Disease (BD). To clarify the mechanisms of innate immune responses, we investigated inflammasome activation in dendritic cells (DC) and neutrophils, following stimulation with two different pattern recognition receptors (PRR) “RIG-1 like” (RLR) and “NOD-like” (NLR) in patients with BD. Methods: Sixteen active BD patients with mucocutaneous lesions and 17 healthy controls (HC) were included in this study. Dendritic cells were generated from monocytes. DCs and isolated neutrophils were activated by RLR and NLR ligands. Caspase-1 activation and expressions of p38 and RIP2 were determined by flow cytometry. Levels of IL-1ß, IL-6, TNF-?, IFN-? and IL-18 in culture supernatants were measured by ELISA. Results: Activation of caspase-1 following intracellular PRR stimulation was found to be in similar levels in DCs and neutrophils of BD patients compared to HC. However, activation of DCs from BD patients to NOD2 stimulus measured with the expressions of RIP2, p38 as well as IL-18 levels was found to be slightly defective (p

Objective. The pathogenesis of Behcet's disease (BD), an inflammatory disease with multisystem involvement, remains poorly understood. This study was undertaken to investigate whether there are DNA methylation abnormalities in BD that might contribute to the pathogenesis of the disease. Methods. We examined genome-wide DNA methylation patterns in monocytes and CD4+ T cells from 16 male patients with untreated BD and age, sex, and ethnicity-matched healthy controls. Additional samples were collected from 12 of the same BD patients after treatment and achievement of disease remission. Genome-wide DNA methylation patterns were assessed using the Infinium Human Methylation 450 BeadChip array, which includes >485,000 individual methylation sites across the genome. Results. We identified 383 CpG sites in monocytes, and 125 in CD4+ T cells, that were differentially methylated between BD patients and controls. Bioinformatic analysis revealed a pattern of aberrant DNA methylation among genes that regulate cytoskeletal dynamics, suggesting that aberrant DNA methylation of multiple classes of structural and regulatory proteins of the cytoskeleton might contribute to the pathogenesis of BD. Further, treatment of BD modified the differences in DNA methylation observed in patients compared to controls; indeed, among CpG sites that were differentially methylated after disease remission versus before treatment, there was widespread reversal of the direction of aberrant DNA methylation observed between the patient and control groups. Conclusion. The results of this epigenome-wide study-the first such study in BD-provide strong evidence that epigenetic modification of cytoskeletal dynamics underlies the pathogenesis of BD and its response to treatment.