P31: Use of omics technology for the identification of critical mediators and pathways in patients with hidradenitis suppurativa

R. Hambly,^1,2 S. Gatault,^3,4 L. Iglesias Martinez,³ S. Kearns,⁵ H. Rea,⁵ V. Marasigan,⁵ K. Lynam-Loane,⁵ S. Kirthi,¹ W. Kolch^3,6 and B. Kirby^1,2,4

¹The Charles Centre, Department of Dermatology, St Vincent’s University Hospital; ²University College Dublin School of Medicine and Medical Sciences; ³Systems Biology Ireland, School of Medicine, University College Dublin; ⁴Charles Institute of Dermatology, School of Medicine, University College Dublin; ⁵Clinical Research Centre, St Vincent’s University Hospital; and ⁶Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with associated systemic inflammation, increased all-cause mortality and impaired quality of life (QoL). Pathogenesis is multifactorial, incorporating genetics, microbiome, physiological/environmental factors, follicular occlusion and immune dysregulation. Treatment options are limited. Adalimumab is the only licensed treatment and is effective in approximately 50% of patients. This was an investigator-led, open-label, single-arm clinical trial of adalimumab in patients with moderate-to-severe HS. Patients underwent clinical assessment and skin biopsies at 0 and 12 weeks. Whole-cell RNA sequencing was completed on biopsies. The primary objective was to examine inflammatory profiles in skin before and after 12 weeks of treatment with adalimumab, using RNA sequencing. Secondary objectives were clinical response (HiSCR), effects on Dermatology Life Quality Index (DLQI), and to identify if responders had a different immunological profile to nonresponders. Twenty patients were enrolled and 19 completed the study. Mean patient age was 37 years and 85% of participants were female. Participants had moderate-to-severe HS, defined as Hurley stage II (60%) or stage III (40%). HiSCR was achieved in 53%. QoL improved with treatment, with a mean DLQI of 17/30 at baseline and 11/30 at week 12. In total, 4000 differentially expressed genes (DEGs) were identified between lesional and nonlesional skin. S100A7, S100A9 and SERPINB4, which have previously been identified as abnormal in HS, were in the top 10 DEGs. We identified significant differences in pathways relating to immune cell functions in lesional compared with nonlesional skin, using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, including regulation of immune response; complement activation; T-cell differentiation, signalling and activation; nuclear factor kappa B signalling; and cytokine–cytokine receptor interaction. We did not identify statistically significant DEGs in lesional skin between weeks 0 and 12. We found higher pretreatment levels of chemokine (C-C motif) ligand 20 (CCL20) in those who responded to adalimumab. CCL20 is known to be overexpressed in HS. Preliminary transcriptomics has identified differences between lesional and nonlesional skin, predominantly relating to immune function. Differences in gene expression were identified at baseline between adalimumab responders and nonresponders, identifying CCL20 as a potential biomarker of treatment response. Further analysis is ongoing, with a particular focus on known pathogenic pathways in HS.

Funding sources: this project was conducted with the financial support of Science Foundation Ireland and AbbVie under the SFI Strategic Partnership Programme Grant Number 15/SPP/3257.

Conflicts of interest: R.H. is currently supported by an academic training grant under the Irish Clinical Academic Training Programme, supported by the Wellcome Trust and the Health Research Board (grant no. 203930/B/16/Z).