HS as an Auto-Inflammatory Disease Study

Hidradenitis suppurativa is an auto‐inflammatory disease: results of an ex vivo study

 

Immune dysregulation, carrying a strong IL‐1 signature, is implicated in the pathogenesis of hidradenitis suppurativa (HS). Interleukin 1 production is based on activation of auto‐inflammatory pathways including the inflammasome, and consequential induction of various cytokines and chemokines. The objective of this study was to determine whether the lesional HS cytokine protein and gene expression profiles could be mimicked/induced by stimulation of perilesional HS skin with IL‐1α and IL‐1ß.

 

Skin punch biopsies from normal appearing perilesional HS skin (HSP) were obtained from 10 HS patients and compared with five skin samples from healthy controls (NN) . All samples were cultured for 24 h in a transwell system using a culture media and media containing either IL‐1α 10 ng/mL or IL‐1ß 10 ng/mL. Subsequently pro‐inflammatory cytokine protein levels in the culture media using a customised 16‐Plex Assay (Luminex) and mRNA expression of four pro‐inflammatory markers in the skin biopsies using real‐time quantitative PCR were analysed. First, the Mann‐Whitney U test was used to compare protein concentrations in the culture media of HSP with NN skin. Second, the Wilcoxon signed rank test was used to pairwise compare stimulated conditions to a condition without stimulation, i.e. culture media (fold change = 1.00).

 

Overall 62.5% (10/16) of the inflammatory proteins were significantly elevated in HSP skin compared with NN skin. After stimulation with IL‐1α or IL‐1ß respectively 40.0% (6/15) and 78.6% (11/14) of the inflammatory proteins were significantly elevated in NN skin compared with 7.1% (1/14) and 38.5% (5/13) in HSP skin. Similar results were found for mRNA expression levels in stimulated HSP and NN skin. Altogether, cytokine levels in HSP skin are already upregulated and almost not further inducible by IL‐1.

 

This study reveals the auto‐inflammatory nature of HS, characterized by the spontaneous increased production of a broad range of pro‐ and anti‐inflammatory cytokines. Our results show that IL‐1ß is a more potent stimulus compared with IL‐1α in both NN and HSP skin.

 

IMMUNOLOGY

008 OS02‐01 ‐ oral session

A. R. J. V. Vossen, K. R. van Straalen, E. Florencia, E. P. Prens

Erasmus University Medical Center, Department of Dermatology, Rotterdam, The Netherlands

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