B-cell and complement signature in severe hidradenitis suppurativa that does not respond to adalimumab.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with significant morbidity. The pathogenesis remains incompletely understood although immune dysregulation plays an important role. It is challenging to treat and approximately 50% of patients respond clinically to adalimumab, the only licensed treatment. OBJECTIVES: To examine differences between lesional and nonlesional HS skin at baseline using bulk RNA sequencing, and to compare the transcriptome in the skin before and after 12 weeks of treatment with adalimumab. To examine transcriptomic differences between adalimumab responders and nonresponders using Hidradenitis Suppurativa Clinical Response and the International Hidradenitis Suppurativa Severity Score System (IHS4); and to compare transcriptomic differences based on disease severity (Hurley stage and IHS4). METHODS: We completed bulk RNA sequencing on lesional and nonlesional skin samples of patients before and after 12 weeks of treatment with adalimumab. RESULTS: Baseline differentially expressed genes and pathways between lesional and nonlesional skin highlighted chemokines and antimicrobial peptides produced by keratinocytes; B-cell function; T-cell-receptor, interleukin-17 and nuclear factor-κB signalling; and T-helper-cell differentiation. Transcriptomic differences were identified in lesional skin at baseline, between subsequent responders and nonresponders. Patients with severe HS who did not respond to adalimumab had enriched complement and B-cell activation pathways at baseline. In addition, logistic regression identified CCL28 in baseline lesional HS skin as a potential biomarker of treatment response. CONCLUSIONS: This highlights the potential for targeting B-cell and complement pathways in HS treatment and the potential of stratifying patients at baseline to the most suitable treatment based on the skin transcriptome. CCL28 has not previously been identified in HS skin and has potential clinical relevance due to its antimicrobial function and homing of B and T cells at epithelial surfaces. Our results provide data to inform future translational and clinical studies on therapeutics in HS.

A Review of Cutaneous Microdialysis of Inflammatory Dermatoses.

Microdialysis is a minimally invasive technique to study metabolic, biochemical, and pharmacological events in tissue. Factors that influence microdialysate collection include molecular weight cutoff of the membrane, perfusion rate, perfusate viscosity, duration of collection, depth of the catheter, length of the tubing and adsorption of hydrophobic molecules to the membrane. To standardize these factors, a robust sampling protocol needs to be established. Microdialysis is applied in healthy and inflamed skin. It enables the in vivo sampling of endogenous and exogenous substances in skin's extracellular fluid. In atopic dermatitis, levels of neuropeptides, eicosanoids and histamine pre- and post-treatment treatment have been conducted. Microdialysis in atopic skin has assessed the pharmodynamics of a number of topical drugs. In psoriatic skin, the 'cytokine fingerprint' has been evaluated through microdialysis and bioassays. This unique fingerprint has also been analyzed after certain pharmacological treatments for psoriasis.