Alterations in Pathways

Alterations in pathway activation found in hidradenitis suppurativa

Shanmugam VK, et al. Clin Exp Dermatol. 2019;doi:10.1111/ced.13959.


May 6, 2019


Biological pathways are disrupted among patients with hidradenitis suppurativa, which suggests that inflammatory pathways, pathways of leucocyte activation and signaling, and innate immune responses require more study, according to researchers.


“This highlights the importance of the immune system in [hidradenitis suppurativa] and identifies deficient or suppressed antimicrobial peptide levels as a possible biomarker in [hidradenitis suppurativa],” Victoria K. Shanmugam, MD, of the division of rheumatology at George Washington University School of Medicine and Health Sciences, told Healio Dermatology.


Researchers measured mRNA expression from skin samples of 10 patients with hidradenitis suppurativa enrolled in the WE-HEAL study and 11 patients with abdominoplasty (healthy controls).


Dermcidin, an antimicrobial peptide normally found in human sweat, had the greatest fold change in hidradenitis suppurativa over control subjects and was significantly downregulated in the hidradenitis suppurativa specimens.


Interleukin-37 was significantly downregulated and found to be one of the top 25 differentially expressed genes, according to researchers.


Thirty canonical pathways in the hidradenitis suppurativa samples showed significant differential expression with normal skin.


Moreover, the IFN-signaling pathway showed differential expression in 19 of 36 molecules, they found.


Among hidradenitis suppurativa samples, molecules in the NFAT pathway were significantly differentially expressed with 11 downregulated and 33 upregulated (z score = 3.68; P < .001), according to researchers.


“At the [George Washington] Hidradenitis Clinic, we have a multidisciplinary team of experts focused on improving the care of patients with hidradenitis. Our team is working on a number of projects investigating the impact of immunosuppressive medications and surgical interventions for [hidradenitis suppurativa],” Shanmugam said.


They are also investigating the interplay of the host immune response and the microbiome in hidradenitis suppurativa and other genetic and molecular drivers of hidradenitis suppurativa, Shanmugam said.


“The interferon inflammatory pathway, pathways of leucocyte activation and signaling, and innate immune responses merit additional investigation as potential drivers of [hidradenitis suppurativa] pathogenesis,” the researchers wrote. – by Abigail Sutton.


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