A Genome‐Wide Survey of DNA Methylation Status in Whole Blood of Patients With Hidradenitis Suppurativa Suggests Systemic Immune Dysregulation and Systemic Disease Burden

ABSTRACT Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a significant systemic disease burden. In this study, we profiled and compared the DNA methylation patterns in whole blood of HS patients versus control subjects to identify associated genes and biological pathways enriched in HS patients that may explain the systemic immune dysregulation observed in these patients. Using the Illumina 850 methylation BeadChip array, we measured the genome‐wide DNA methylation status of each subject and identified 16 variably methylated probes (VMPs) between control subjects and HS patients ( p adj < 0.05). These VMPs were associated with genes that regulate immune responses (e.g. DEFB104B , GRAMD4 ) and drive the risk of malignancy (e.g. BCR , RNF4 ). Additionally, they annotated to downstream biological pathways that regulate both innate and adaptive immunity, including the interferon gamma signalling pathway. Taken together, our results suggest a potential role of epigenetics in regulating the expression of immune‐regulatory/tumour suppressor genes in the systemic circulation of HS patients.