Poster abstracts
which reached PSI75 at week 12 and PASI90 at week 24. At the
time of this writing, one year after the initiation of treatment, the
patient remains almost clear from her psoriatic lesions. Apremilast
was well-tolerated by the patient.
Conclusions: The treatment of moderate-to-severe psoriasis in the
background of chronic HBV limits the therapeutic options due
to the possibility of HBV reactivation when the psoriasis patient
is treated with immunosuppressive or even immunomodulatory
drugs. Apremilast is an oral small-molecule PDE-inhibitor, appro-
ved by the Food and Drug Administration for the treatment of
moderate-to-severe- plaque psoriasis in 2014. It does not target
any one cytokine but restores a balance of pro-inflammatory and
anti-inflammatory mediators. The pharmacokinetics of Apre-
milast is not affected by hepatic impairment and the drug is not
hepatotoxic. Moreover, it is not contraindicated in patients with
active infection. To our knowledge, this is the first reported case
of Apremilast psoriasis patient with chronic inactive Hepatitis B.
It proved to be both safe and efficacious but large, well-organized
studies are needed in order to confirm this conclusion.
P098
IL-22 INDUCES KERATINOCYTES
HYPERPROLIFERATION IN PSORIASIS VIA MIR-21
AND MIR-31 UPREGULATION
Florence Abdallah
Centre de Biophysique Moléculaire, CNRS UPR4301, Orléans, France
Psoriasis is a chronic inflammatory skin disease that affects
people of all ages with an estimated 3% prevalence worldwide.
It manifests as thick red irritated skin lesions due to imbalanced
keratinocytes hyperproliferation and differentiation caused mainly
by increased activation of IL-22 pathway in keratinocytes. Emer-
ging studies showed a specific psoriatic miRs signature where
miR-21 and miR-31 are one of the most upregulated miRs. The
latters act by favoring cellular proliferation and inflammation.
Hence, re-conciliating the microRNAs and the immunopathogenic
occasions responsible for psoriasis development can be a new
approach for developing effective mechanism and target-based
agents to treat psoriasis.
The common hyper-proliferation effect of IL-22, miR-21 and
miR-31 prompted us to look after a potential interaction between
these actors. The expression levels of those 2 microRNAs and that
of their targets were evaluated both in vitro and in vivo studies in
presence or absence of IL-22.
We first exploited different skin models to investigate a potential
connection between IL-22 and miR-21 or miR-31. The qPCR
analysis showed a significant increase in the relative expression
(RE) of both miRs in the different models upon IL-22 stimula-
tion during 24h compared to untreated cells. These observations
indicate the implication of miR-21 and miR-31 in proliferation-
differentiation processes in the different layers of the epidermis.
We also examined the miR-21 target RE PTEN involved in cell
growth and apoptosis control and the miR-31 target RE ppp6c
involved in G1 to S phase transition restriction. In line with the
upregulation of miR-21 and miR-31, IL-22 stimulation resulted
in significant downregulation of both targets at the genomic and
proteomic levels.
We next investigated the in vivo correlation between IL-22 and
miR-21 or miR-31 respectively in the development of psoriatic
lesion. We used the imiquimod-induced psoriasiform skin inflam-
mation in Wild type and IL-22 deficient mice (known to be almost
protected from IMQ). Mice displaying a less severe disease form
had less miR-21 expression. By contrast, WT mice treated with
IMQ exhibited significantly higher miR-21 RE than IL-22-/- mice.
Furthermore, miR-31 expression in IL-22-/- mice was identical to
miR-31 expression in WT control mice. These results suggest a
41
direct correlation between IL-22 pathway and miR-31 epidermal
expression. In line with these observations, the miR targets (PTEN
and ppp6c) were contrariwise proportional to miRs expression
confirming by that the specificity of the IL-22/miR-21 and IL-22/
miR-31 correlation.
These findings identify IL-22 as a key regulator of miRs implica-
ted in multiple signaling pathways that coordinate keratinocytes
proliferation activity
P099
SERUM CONCENTRACION OF IFN-GAMMA IN
PATIENTS WITH PSORIASIS: CORRELATION WITH
CLINICAL TYPE AND SEVERITY OF DISEASE
Nermina Ovčina-Kurtović, Emina Kasumagić-Halilović, Jasmina
Muhović
Dermatovenerology Department Clinical center University