Forum for Nordic Dermato-Venereology Nr 2, 2018 | Page 18

Charlotta Enerbäck – Ingrid Asp Psoriasis Research Center
not reduced by the commonly used UV therapy. Patients with
psoriasis and cardiovascular risk may therefore benefit from
systemic treatment rather than UV therapy (13, 14).
References
Fig. 2. Unsupervised hierarchical clustering of methylation ratios shows
a distinct separation of the uninvolved and healthy epidermis. yellow:
hypermethylation, red: hypo methylation.
million CpG sites in the epidermal DNA. Our findings suggest
the overall hypermethylation of the involved and uninvolved
psoriatic epidermis compared with the healthy epidermis and
reveal a large number of sites whose methylation pattern
differs between the separate conditions. In particular, we
have observed the differential methylation pattern in several
psoriasis risk-associated loci, IL23R, TRAF3IP2 and TNFAIP3.
Interestingly, we detect a specific methylation pattern in un-
involved skin compared with normal skin (12).
Studies of the cardiovascular comorbidites in pso-
riasis
These studies are part of Gunna Sigurdardottir’s thesis. She
will defend her thesis in 2018.
We have screened a panel of cardiovascular and inflammatory
markers for their utility as biomarkers. Using Luminex technol-
ogy, we have analysed a large number of markers related to the
metabolic syndrome and endothelial dysfunction in psoriasis
patients and body mass index (BMI)-matched controls. Among
them, thrombomodulin and plasminogen activator inhibitor-1
(PAI-1) were found to be significantly altered, which we an-
alyse further in independent samples. The levels of some of
these markers were effectively diminished by treatment with a
tumour necrosis factor alpha (TNF-a) inhibitor, but they were
48
D ermato -V enereology in the N ordic C ountries
1. Madsen P, Rasmussen HH, Leffers H, Honoré B, Dejgaard K, Olsen
E, et al. Molecular cloning, occurrence, and expression of a novel
partially secreted protein “psoriasin” that is highly up-regulated
in psoriatic skin. J Invest Dermatol 1991; 97: 701–712.
2. Krop I, März A, Carlsson H, Li X, Bloushtain-Qimron N, Hu M, et
al. A putative role for psoriasin in breast tumor progression. Cancer
Res 2005; 65: 11326–11334.
3. Vegfors J, Ekman AK, Stoll SW, Bivik Eding C, Enerbäck C. Psoriasin
(S100A7) promotes stress-induced angiogenesis. Br J Dermatol
2016; 175: 1263–1273.
4. Shubbar E, Vegfors J, Carlström M, Petersson S, Enerbäck C. Psori-
asin (S100A7) increases the expression of ROS and VEGF and acts
through RAGE to promote endothelial cell proliferation. Breast
Cancer Res Treat 2012; 134: 71–80.
5. Ekman AK, Vegfors J, Eding CB, Enerbäck C. Overexpression of
psoriasin (S100A7) contributes to dysregulated differentiation in
psoriasis. Acta Derm Venereol 2017; 97: 441–448.
6. Eding C.B, and Enerback. Involved and uninvolved psoriatic ke-
ratinocytes display a resistance to apoptosis that may contribute
to epidermal thickness. Acta Derm Venereol 2017; 97: 788-796.
7. Gad H., et al. MTH1 inhibition eradicates cancer by preventing
sanitation of the dNTP pool. Nature 2014; 508: 215-221.
8. Dand N, et al. Exome-wide association study reveals novel pso-
riasis susceptibility locus at TNFSF15 and rare protective alleles
in genes contributing to type I IFN signalling. Hum Mol Genet
2017; 26: 4301-4313.
9. Carlström M, Ekman AK, Petersson S, Söderkvist P, Enerbäck C.
Genetic support for the role of the NLRP3 inflammasome in pso-
riasis susceptibility. Exp Dermatol 2012; 21: 932–937.
10. Ekman AK, Verma D, Fredrikson M, Bivik C, Enerbäck C. Genetic
variations of NLRP1: susceptibility in psoriasis. Br J Dermatol 2014;
171: 1517–1520.
11. Enerback C, et al. The psoriasis-protective TYK2 I684S variant
impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+
and CD8+ memory T-cells. Sci Rep 2018; 8. 7043.
12. Verma D, et al. Genome-Wide DNA Methylation Profiling Identi-
fies Differential Methylation in Uninvolved Psoriatic Epidermis.
J Invest Dermatol 2017.
13. Ekman AK, Sigurdardottir G, Carlström M, Kartul N, Jenmalm MC,
Enerbäck C. Systemically elevated Th1-, Th2- and Th17-associated
chemokines in psoriasis vulgaris before and after ultraviolet B
treatment. Acta Derm Venereol 2013; 93: 527–531.
14. Sigurdardottir G, Ekman AK, Ståhle M, Bivik C, Enerbäck C. Sys-
temic treatment and narrowband ultraviolet B differentially affect
cardiovascular risk markers in psoriasis. J Am Acad Dermatol 2014;
70: 1067–1075.
Forum for Nord Derm Ven 2018, Vol. 23, No. 2