Acta Dermato-Venereologica Suppl 219 AbstractPsoriasis2018 | Page 46

44 5 th World Psoriasis & Psoriatic Arthritis Conference 2018 mental factors may contribute to autoimmunity in psoriasis. TCRs are known to be polyspecific, recognizing multiple peptide ligands which share a conserved amino acid pattern specific for each TCR. Objectives: To examine the potential role of environmental factors in the psoriatic autoimmune response. Methods: We first determined the particular amino acid motif which is recognized by the psoriatic Vα3S1/Vβ13S1 TCR in the context of HLA-C*06:02. By homology searches using this conserved amino acid pattern, we selected 57 peptides from food, bacterial, fungal and viral pathogens and from the skin and intestinal microbiomes as candidate environmental antigens that may trigger the psoriatic autoimmune response. We cloned the peptides into expression plasmids, co-transfected them with HLA- C*06:02 into Cos7 cells and used them to stimulate the Vα3S1/ Vβ13S1 TCR. TCR ligation was determined by GFP induction of TCR hybridoma in FACS analysis. We then stimulated blood lymphocytes with the candidate peptides that had ligated the Vα3S1/Vβ13S1 TCR. Lymphocyte activation was assessed by induction of activation markers and proliferation assays using thymidine incorporation. Results: We identified a variety of peptides contained in proteins from food (wheat, coffee, apple, and spinach), microbiota of hu- man skin or gut, and infectious pathogens including Chlamydia trachomatis, which ligated the psoriatic TCR in a polyspecific manner. Stimulation of blood lymphocytes with particular candi- date antigens resulted in significant activation in psoriasis patients, as compared to healthy individuals. Interindividual-correlation analyses demonstrated cross-reactive immune responses between environmental antigens and the melanocyte autoantigen presen- ted by HLA-C*06:02 in psoriasis patients. Among the candidate antigens, wheat peptides induced most robust lymphocyte activa- tions in psoriasis patients. Moreover, psoriasis was significantly improved by wheat-free diet in several patients with lymphocytes responding to wheat, indicating potential pathogenic contribution of wheat antigens in psoriasis. Conclusions: Our results provide unbiased evidence that several environmental antigens may trigger the melanocyte-specific autoimmune response in psoriasis. By identifying and avoiding those triggers at the molecular level which translate the genetic predisposition into disease manifestation, we may develop stra- tegies to prevent disease onset and exacerbation. P107 A SKEWED POOL OF RESIDENT T CELLS TRIGGERS DISEASE-ASSOCIATED TISSUE RESPONSES IN NEVER- LESIONAL PSORIASIS Irène Gallais Sérézal 1 , Elena Hoffer 1 , Borislav Ignatov 1 , Elisa Martini 1 , Beatrice Zitti 2 , Marcus Ehrström 3 , Liv Eidsmo 1 Department of Medicine Solna, Karolinska Institutet, 2 Centre for Haema- tology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 3 Department of Re- constructive Plastic Surgery, Karolinska University Hospital Solna, Stock- holm, Sweden 1 Background: Psoriasis lesions evolve as a result of cytokine driven interactions between intralesional immune cells and keratinocytes in genetically predisposed individuals. Skin resident T cells are implicated in maintenance and recurrence of psoriasis plaques but their composition and function in never-lesional psoriasis skin is less known. Objective:Characterisation of T cell driven tissue responses and subsets of resident T cells in never-lesional psoriasis. Methods: T cell driven tissue responses were assessed in explanted skin biopsies using Nanostring and Multiplex analysis. Epidermal and dermal T cells were characterised using flow cytometry in never-lesional skin from patients with mild disease. Results: T cell activation induced epidermal psoriasiform- and type-1 interferon tissue responses in explants from never-lesi- www.medicaljournals.se/acta onal skin. Skin resident T cells were skewed with enrichment of epidermal IL-17 and IL-22 producing CD4+CCR6+ and CD8+CD103+CD49a- T cells and IFN-γ producing CD4 T cells in never-lesional skin compared to healthy skin. Keratinocytes from never-lesional psoriasis responded to IFN-γ activation with IFN-α secretion and MX1 upregulation and skin explants exposed to common fungal antigens produced the CCR6-attractant CCL20. Conclusion: Resident T cells poised to induce psoriasiform tissue responses accumulate in never-lesional skin of psoriasis-afflicted individuals. Additionally our data suggest that microbial interplay with genetically predisposed keratinocytes may shape the local pool of resident T cells. References: Verma, D., Ekman, A.-K., Bivik Eding, C. & Enerbäck, C. Genome-Wide DNA Methylation Profiling Identifies Differential Methylation in Unin- volved Psoriatic Epidermis. J. Invest. Dermatol. (2017). doi:10.1016/j. jid.2017.11.036 Gudjonsson, J. E. et al. Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvol- ved psoriatic skin. J. Invest. Dermatol. 129, 2795–2804 (2009). Cheuk, S. et al. Epidermal Th22 and Tc17 Cells Form a Localized Disease Memory in Clinically Healed Psoriasis. J. Immunol. 192, 3111–3120 (2014). P108 NAIL INVOLVEMENT IN PSORIASIS; IS IT A PREDICTOR OF PSORIATIC ARTHRITIS? Omid Zargari 1 , Ehsan Kazemnejad 2 , Seyyede Zeinab Azimi 3 Department of Dermatology, Skin Research Center, Shahid Beheshti Uni- versity of Medical Sciences, Tehran, 2 Department of Biostatistics, 3 Depart- ment of Dermatology, Guilan University of Medical Sciences, Rasht, Iran 1 Introduction: Psoriatic Arthritis (PsA) arises in an increased burden of psoriasis and impairments in both quality of life and functional capacity. The relationship between nail involvement and PsA in psoriasis is not fully characterized. Objective:To evaluate the frequency and characteristics of nail involvement in psoriatic patients and to assess