797
SHORT COMMUNICATION
Soluble Receptor for Advanced Glycation End Products: A Novel Biomarker for Psoriasis Severity with
Therapeutic Implications?
Aleksandra BATYCKA-BARAN, Wojciech BARAN, Danuta NOWICKA-SUSZKO and Jacek C. SZEPIETOWSKI
Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Chalubinskiego 1, PL-50-368, Wroclaw, Poland.
E-mail: [email protected]
Accepted Mar 27, 2018; Epub ahead of print Mar 27, 2018
Psoriasis is a common, chronic, immune-mediated inflam-
matory disease with increased risk of cardiovascular disease
and metabolic disturbances (1).
The receptor for advanced glycation end products (RAGE)
is a multi-ligand, pattern recognition receptor, a member of
the immunoglobulin superfamily. It has the ability to engage
diverse classes of ligands, including S100 proteins and ad-
vanced glycation end products. RAGE-ligand interactions
have been shown to amplify and perpetuate the chronic im-
mune-mediated inflammatory process by sustained activation
of transcription factor kappa beta (NF-κβ). RAGE-mediated
signalling triggers expression of adhesion molecules, pro-
inflammatory cytokines (e.g. tumour necrosis factor alpha
(TNF-α), interleukin (IL)-1, -6, and -8) and recruitment of
inflammatory cells to the site of inflammation (2, 3). Further-
more, the activation of RAGE appears to have a central role
in accelerating atherosclerosis (2, 4, 5). The potential of the
RAGE-ligand axis as a target of future therapeutic inter-
vention has been proposed (2, 4–7). The full-length form
of RAGE (fl-RAGE) is a transmembrane receptor. Soluble
RAGE (sRAGE) is a truncated form of RAGE, lacking the
transmembrane and cytoplasmic domains. sRAGE is deri-
ved predominantly from proteolytic cleavage of fl-RAGE.
sRAGE acts as an extracellular decoy receptor, antagoni-
zing fl-RAGE by binding its ligands without mediation of
any cellular activity (2–4). Therefore, it is postulated that
sRAGE has protective properties in chronic inflammatory
diseases and atherosclerosis (2, 3, 4, 8). Low sRAGE levels
have been found in atherosclerosis, cardiovascular disease,
vascular complications of diabetes and in some chronic
immune-mediated disorders, such as rheumatoid arthritis.
A decreased sRAGE level has been proposed as a marker
for chronic inflammation and atherosclerosis (2, 3, 4, 8–10).
The objective of the present study was to determine, for
the first time, levels of sRAGE in individuals with chronic
plaque psoriasis. The associations between sRAGE levels,
severity of psoriasis, levels of C-reactive protein (CRP) and
some clinical data have been evaluated.
METHODS
The study was conducted on a group of 65 consecutive patients
with chronic plaque psoriasis, aged from 18 to 76 years. A total of
35 healthy volunteers, matched by age and sex, randomly selec-
ted, with no history of psoriasis served as controls. Subjects with
psoriasis did not receive any systemic therapy and phototherapy at
least 4 weeks prior to initiation of the study and have never been
treated with biologics. Severity of skin disease was assessed with
the Psoriasis Area and Severity Index (PASI) by a single, expe-
rienced dermatologist. Exclusion criteria included: cardiovascular
disease (defined as history of coronary artery disease, myocardial
infarction, stroke, peripheral artery disease), chronic renal or liver
disease, diabetes mellitus, malignancies and infectious diseases.
Patients with psoriatic arthritis, diagnosed according to the
ClASsification criteria for Psoriatic ARthritis (CASPAR), were
excluded from the study. Information regarding the presence of
traditional cardiovascular risk factors (e.g. arterial hypertension
(HA), obesity, dyslipidaemia, smoking habit) and medication
use were documented (Table SI 1 ). The study was approved by
the local Bioethical Committee according to the principles of the
Declaration of Helsinki.
The serum concentration of sRAGE was quantified using
enzyme-linked immunosorbent assay