Skin Disease

Dermcidin, an anti-microbial peptide normally find in human sweat, may play a role in the pathogenesis of this chronic skin disease hidradenitis suppurativa (HS), according to a research team from the George Washington University (GW). Their findings were recently publish in Clinical and Experimental Dermatology.

Skin as a part of the innate host

Dermicidin, also know as proteolysis-inducing factor (PIF); so is a protein that in humans is encode by the DCD gene. It is an anti-microbial peptide secrete by human eccrine sweat glands onto the skin; so as a part of the innate host defense of the immune system. It is also involve in proteolysis.
Dermicidin is a secrete protein that is subsequently process into mature peptides of distinct biological activities. The C-terminal peptide is constitutively express in sweat and has antibacterial and antifungal activities. The N-terminal peptide, also know as diffusible survival evasion peptide; so promotes neural cell survival under conditions of severe oxidative stress. A glycosylated form of the N-terminal peptide may with cachexia (muscle wasting) in cancer patients.

HS is a chronic, recurrent inflammatory disease of the apocrine sweat glands; which impacts 1%-4% of people and is most prevalent in young adults. There are several treatments to help alleviate symptoms; hence however there is no know cure for the disease. Until now, the molecular drivers of HS have poorly understood,” said Victoria Shanmugam, MD, associate professor of medicine at the GW School of Medicine and Health Sciences.

Natural suppressor of innate responses

Traditional therapies have thus far disappointing. However, TNF-α inhibitors like infliximab and adalimumab have shown efficacy. Shanmugam’s team analyze transcriptome patterns; hence in HS skin to identify transcripts and upstream regulators that are differentially express in HS, compare to normal skin. The study find that dermcidin had the greatest fold change in HS and was significantly down regulate in HS specimens.
The team also found that IL37, a cytokine know to a natural suppressor of innate immune responses; hence was down regulate in HS specimens compare to normal controls. These findings suggest regulators of the innate immune response and particularly antimicrobial peptide production may play a role in HS pathogenesis,” Shanmugam said.
The data suggests multiple biological pathways are disrupt in HS, indicating that inflammatory pathways merit additional investigation as potential drivers of the disease. Further study is need, they explain, in order to fully understand the role of antimicrobial peptides, particularly dermcidin, in the pathogenesis of HS and whether these pathways lend themselves to the development of new therapeutic options for the disease.