Epidermolysis bullosa (EB) is a group of rare intractable inherited skin fragility disorders. A broad spectrum of severity is observed but the overarching characteristic is that of blistering inducible by little-to-no trauma, and recurrent, slow-to-heal wounds. Major EB subtypes are grouped by the plane of intraepithelial blistering consequent to the underlying mutation and may be clinically distinguished by key phenotypic features: EB simplex (EBS), Junctional EB (JEB), Dystrophic EB (DEB) and Kindler EB (KEB). Frustrated wound healing is multifactorial with a range of contributory factors including aberrant tissue architecture, dysbiosis, and persistent non-resolving inflammation.
Proteins including cytokines, chemokines and proteases are the principal effectors of wound healing. Cytokines and chemokines influence inflammation and proliferation through orchestrating of immune and stem cell migration to sites of injury, whilst proteases modulate tissue re-modelling and regulation of other proteins. However, there is scant literature examining the nature of inflammation or the proteome within the wound microenvironment across EB subtypes, with a solitary study demonstrating increased expression of pro-inflammatory signalling molecules.
We hypothesised that different EB subtypes are associated with distinct plasma and acute blister fluid proteomic signatures that may influence subsequent wound healing events, with consequent differential clinical outcomes and observed phenotypes. In this pilot study, we undertook paired ELISA-based quantification of serum cytokines and array-based cytokine analysis of fresh (<24 hr) blister fluid harvested across 3 major EB subtypes (EBS, JEB, DEB) and healthy unaffected controls. Contrary to our hypothesis, we observed no significant difference in blister fluid cytokine quantities across EB types or healthy controls, suggesting that common inflammatory pathways underpin the acute response to blister formation. In contrast, greater quantities of IL-8 and TNF-α were identified in serum from JEB patients (though not reaching statistical significance). Further work is underway to validate and investigate the relevance of these findings.