Review Examines Role of Antimicrobial Peptides in Hidradenitis Suppurativa

Hidradenitis suppurativa, which is linked with microbial dysbiosis and immune dysregulation, is defined by recurrent nodules, tunnels and scarring, primarily in skin folds; the review found a multitude of antimicrobial peptides expressed in this skin disease.

A recent literature review examined the role of skin-produced antimicrobial peptides (AMPs) in hidradenitis suppurativa (HS), a chronic, inflammatory skin disease in hair follicles.

HS, which is linked with microbial dysbiosis and immune dysregulation, defined by recurrent nodules, tunnels and scarring, primarily in skin folds. Previous work has shown dysregulated levels of AMPs in HS. AMPs are key defense players in innate immunity and help fight microbial invasion, particularly against Gram-positive and Gram-negative bacteria, as well as some fungal and viral agents. They are also strong immunomodulators and have been implicated in several chronic inflammatory conditions in the epithelium of the intestines, airways, and skin.

Researchers screened PubMed, Embase, and the Cochrane Library, ultimately choosing 18 retrospective and prospective studies published between 2009 and 2020.

Of the 18 studies:

  • 14 analyzed biopsies from lesions
  • 1 study analyzed isolated outer root sheath (ORS) occipital hair follicle keratinocytes from patients
  • 1 study examined whole blood
  • 1 study examined the serum of patients with HS

In addition, 8 studies analyzed both mRNA and protein levels of AMPs; 3 studies only analyzed mRNA levels; 7 studies analyzed protein levels.

For mRNA analysis, most studies used quantitative real-time polymerase chain reactions (qPCR); for protein analysis, most studies used immunohistochemistry (IHC).

Results showed that members of the human β-defensin (hBD) and S100 protein families were the most commonly investigated AMPs. S100 proteins are expressed in the epidermis and regulate of cell proliferation and differentiation.

The studies found a consistent overexpression of hBD-2, S100A7, S100A8 and S100A9 at both the mRNA and protein levels, and a decreased expression of hBD-1. The mechanisms behind the lower levels of hBD-1 in the development of HS remain unclear. Evidence was mixed on the involvement of hBD-3 in HS, with 4 studies reported upregulation of hBD-3 mRNA and protein and 3 studies finding no upregulation of hBD-3 mRNA or protein

Overall, the studies indicate a dysregulation of AMPs in both lesional and nonlesional HS skin.

“Future studies investigating epigenomic, genomic and protein expression are warranted to achieve a more comprehensive view of their potential significance in the pathogenesis of HS,” concluded the authors.

Reference

Yao Y, Frew JW, Thomsen SF, Ring HC. Antimicrobial peptides in hidradenitis suppurativa: A systematic review. Br J Dermatol. Published online September 9, 2021. doi: 10.1111/bjd.207