Poster abstracts
TNFi-induced psoriasis, three patients with SLE and psoriasis,
three patients with positive ANA and psoriasis, two patients with
ICI-induced psoriasis and two patients with chronic plaque psoria-
sis as control. Immunohistochemistry was performed using anti-
bodies against type-1 IFN induced MXA, LL37, IL-36 and CD8 T
cells. The intensity and the area of positively stained samples were
each graded from 0–4 and then multiplied to provide a final score.
Results: Small plaque lesions in various clinical scenarios had his-
tologic changes consistent with psoriasis.. Immunohistochemical
evaluation revealed an increased expression of MXA (TNFi = 14,
SLE = 13.3, ANA = 11.3, ICI = 16 vs. control = 6, t-test p < 0.05),
LL37 (TNFi = 10.8, SLE = 6, ANA = 9.7, ICI = 12 vs. control = 2,
t-test p < 0.05) and IL-36 (TNFi = 10.5, SLE = 13.3, ANA = 11,
ICI = 7, control = 0.25, t-test p < 0.05) in the keratinocytes of
SPP patients. There was decreased CD8 T cell migration to the
epidermis in SPP compared to control.
Conclusion: This is the first study to describe the immune-
phenotype of SPP and to extend the phenotype observed in TNFi
induced psoriasis to varying clinical scenarios. There was an
increased expression of MXA, LL-37 and IL-36 as well as fewer
epidermal CD8 T cells than in chronic plaque psoriasis consis-
tent with the type-1 IFN pathway of psoriasis pathogenesis. This
immune-phenotypic analysis may suggest tailored therapy for
this form of psoriasis.
P104
SERUM GLUCOCORTICOID-INDUCIBLE KINASE-
1(SGK1) LEVELS IN PATIENTS WITH PSORIATIC
ARTHRITIS
Goksal Keskin 1 , Ali Inal 2 , Esra Dilek Keskin 3 , Umit Olmez 1
1
Department of Immunology, Medical School of Ankara University, 2 De-
partment of Immunology, Medical School of Baskent University, 3 Depart-
ment of FTR, Medical School of Kırıkkale University
Introduction: Psoriatic arthritis (PsA) is an inflammatory rheuma-
tic disorder that occurs in patients with psoriasis. The etiology of
PsA is not well understood but evidence supports an interplay of
genetic, immunologic, and environmental factors which promote
pathological bone remodeling and joint damage in PsA. The
glucocorticoid-inducible kinase-1(SGK1) is genomically upre-
gulated by cell stress. However, excessive SGK1 expression and
activity participates in the pathophysiology of several disorders,
such as inflammation, autoimmune disease, fibrosis, hypertension,
thrombosis and tumor growth.
Objectives: In this study, we analyzed the possible role of serum
SGK-1 levels in the pathogenesis of psoriatic arthritis.
Methods: 56 patients with psoriasis (40 patients with psoriatic
arthritis; 16 female, 24 male, mean age; 46.7 ± 6.5 years, mean
disease duration 17.7 ± 4.3 years and 16 patients without arthritis; 8
female, 8 male, mean age; 43.2 ± 1.9 years, mean disease duration;
14.1 ± 3.9 years) and 19 healthy controls (11 female, 8 male; mean
age 41.3 ± 4.7 years) were enrolled in this study. Oligoarthritis was
the commonest clinical presentation (76.4 %). Dactylitis (73.4%)
and enthesitis (48.1%) were frequent extra-articular features.
All patients were negative for rheumatoid factor. HLA-B27 was
negative in 14 patients. Serum SGK-1 levels were determined
by ELISA.
Results: The mean serum SGK-1 levels were 58.4 ± 18.1 pg/ml in
healthy controls, 163.7 ± 27.8 pg/ml in patients without arthritis
and 443.9 ± 32.1 pg/ml in patients with arthritis. Serum SGK-1
levels were significantly high in patients with psoriasis compared
with healthy controls (p < 0.001). Serum SGK-1 levels were sig-
nificantly high in patients with psoriatic arthritis compared with
in patients without psoriatic arthritis (p < 0.001).
Conclusions: The evidence is strong that immunological mecha-
nisms are involved in the pathogenesis of psoriasis. In this study,
we demonstrated that serum SGK-1 levels were significantly
elevated in patients with psoriasis and psoriatic arthritis.
43
P105
DIFFERENTIAL NH2-TERMINAL AUTOANTIGEN
TRIMMING MAY EXPLAIN EPISTASIS BETWEEN
HLA-C*06:02 AND ERAP1 VARIANTS IN PSORIASIS
RISK
Akiko Arakawa 1 , Emma Reeves 2 , Sigrid Vollmer 1 , Yukiyasu Ara-
kawa 1 , Edd James 2 , Jörg Prinz 1
Ludwig-Maximilian-University, 2 Southampton General Hospital
1
Introduction: NH2-terminal trimming by endoplasmic reticulum
aminopeptidase 1 (ERAP1) generates the appropriate length of
antigenic peptides for binding to and presentation by HLA-class
I molecules. Genetic interaction between ERAP1 variants and
HLA-class I alleles determines the genetic risk for various HLA-
class I-associated inflammatory diseases. Epistasis between HLA-
C*06:02 and ERAP1 variants affects also psoriasis risk but the
mechanisms of these gene interactions remained unknown. Using
a pathogenic Vα3S1/Vβ13S1-TCR from a psoriatic CD8+ T-cell
clone we had shown that in psoriasis, HLA-C*06:02 mediates an
autoimmune response against melanocytes through autoantigen
presentation and we had identified a peptide from ADAMTS-like
protein 5 (ADAMTSL5) as HLA-C*06:02-presented melanocyte
autoantigen.
Objectives: To determine the role of ERAP1 variants in psoriasis
pathogenesis.
Methods: We established ERAP1 knockout cells using CRISPR/
Cas9 system. ERAP1 knockout cells transfected with plasmids
coding for HLA-C*06:02, ERAP1 variants, and antigenic pep-
tides were co-cultured with the TCR hybridoma to determine
the levels of TCR ligation which reflect the generation of the
antigenic ADAMTSL5 peptide and other Vα3S1/Vβ13S1-TCR
ligands from precursors.
Results: Our data show that NH2-terminal trimming by ERPA1
is required to generate the actual antigenic ADAMTSL5 peptide
from NH2-terminally elongated precursors. An ERAP1 variant
protecting from psoriasis reduced the immunogenicity of the
antigenic ADAMTSL5 peptide presumably through overtrimming
and peptide destruction, whereas a psoriasis risk variant of ERAP1
highly kept the antigenicity of the autoantigen. This effect was
specific for ADAMTSL5. Precursors of other Vα3S1/Vβ13S1-
TCR self-ligands were not substrates of ERAP1.
Conclusions: Using a proven psoriatic autoantigen and a cognate
psoriatic TCR, these experiments provide direct evidence that
gene-gene interaction between ERAP1 and HLA-C*06:02 affects
the risk for psoriasis through differential autoantigen trimming
from precursors. These data furthermore propose a model where
ERAP1 function essentially controls the autoantigenic potential
of self-peptides in HLA-class I associated CD8+ T-cell mediated
autoimmune diseases.
P106
ENVIRONMENTAL TRIGGERS OF AN HLA-C*06:02-
RESTRICTED AUTOIMMUNE RESPONSE IN PSORIASIS
Secil Vural, Yukiyasu Arakawa, Adrian Galinski, Sigrid Vollmer,
Akiko Arakawa, Jörg Prinz
Ludwig Maximilian University
Introduction: Psoriasis vulgaris is a multifactorial disease. While
the major psoriasis risk gene HLA-C*06:02 accounts for up to
50% of disease onset, environmental factors are considered to
contribute to approximately 30% of disease risk. Psoriatic skin
inflammation is driven by an HLA-C*06:02-mediated autoimmune
response against melanocytes. A pathogenic Vα3S1/Vβ13S1 T-cell
receptor (TCR), which we had reconstituted from a lesional epi-
dermal CD8 + T-cell clone of an HLA-C*06:02–positive psoriasis
patient in a mouse reporter hybridoma cell line, specifically reacts
against melanocytes through HLA-C*06:02 restricted recognition
of a psoriatic melanocyte autoantigen, ADAMTS-like protein 5
(ADAMTSL5). However, it is unknown whether and how environ-
Acta Derm Venereol 2018