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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