521 Deciphering Pathomechanisms in Solar Urticaria

Solar Urticaria (SU) is a rare, chronic inducible urticaria characterised by an itching or burning erythemal flare with without whealing, that can develop within minutes of exposure to ultraviolet radiation (UVR) and/or visible light. It hypothesised unidentified endogenous photo-allergen may be the trigger, leading IgE-mediated mast cell degranulation. However, evolution response and mechanisms involved are not well understood. We undertook UVR provocation study transcriptome analysis examine early events in SU pathophysiology. Patients diagnosed (n=4) were provoked on photoprotected upper buttock skin 10J/cm2 solar simulated UVR. Skin biopsies taken 30min, 3h 24h post from adjacent unexposed skin. A comparator group healthy volunteers underwent same biopsy protocol. samples analysed RNAseq immunofluorescent staining. Transcriptomic revealed activation inflammation DAMP signalling pathways patients but controls across all time points. Upstream regulator highlighted TNFα, Toll-like receptors, several interleukins. Immunofluorescence showed extracellular release TNFα was significantly higher as 30 UVR, (P=0.01). Notably, causal predicted down-regulation transcription factor DLX3 compared controls. staining observably lower levels epidermal Our data show involve chemotactic inflammatory following single which seen Baseline differences production indicate possible disruption homeostasis patients. Further these will aid understanding underlying potential identify new therapeutic targets.