Acta Dermato-Venereologica 99-6CompleteContent | Page 15
INVESTIGATIVE REPORT
Serum miR-125a-5p and CCL17 Upregulated in Chronic
Spontaneous Urticaria and Correlated with Treatment Response
Liming ZHANG, Ruiqun QI, Yang YANG, Xinghua GAO, Hongduo CHEN and Ting XIAO
Department of Dermatology, The First Hospital of China Medical University, National Health Commission Key Laboratory of Immunodermatology,
Key Laboratory of Immunodermatology of Ministry of Education, Shenyang, China
Chronic spontaneous urticaria (CSU) is a common
skin disorder associated with autoimmunity. Micro
RNAs (miRNAs) are endogenous noncoding RNA mo-
lecules reported to be potential biomarkers for some
autoimmune diseases. In this study, we investigated
the association of miRNAs with CSU. A quantitative
PCR (qPCR)-based array was generated from sera as
obtained from 20 active CSU patients and 20 healthy
controls. Upregulated or downregulated miRNAs were
validated by reverse transcription qPCR in sera from
59 active CSU patients and 58 healthy controls. The ex-
pression of miR-125a-5p was significantly upregulated
in CSU sera and serum levels of CCL17 were also signi-
ficantly increased in CSU patients. Serum miR-125a-5p
expressions were found to be further upregulated in
refractory CSU cases (n = 10). In 12 CSU patients in
remission, serum miR-125a-5p expression and CCL17
levels were significantly decreased as compared with
that obtained in active phase patients. These results
indicated that miR-125a-5p and CCL17 can serve as
potential serum biomarkers for CSU.
Key words: chronic spontaneous urticaria; chronic idiopathic
urticaria; miR-125a-5p; CCL17; IL-17.
Accepted Feb 26, 2019: E-published Feb 27, 2019
Acta Derm Venereol 2019; 99: 571–578.
571
Corr: Ting Xiao and Hongduo Chen, Department of Dermatology,
The
First Hospital of China Medical University, No. 155 Nanjing Bei Street,
Shenyang 110001, China.
E-mails: [email protected]; hongduochen@
hotmail.com.
C
hronic spontaneous urticaria (CSU) is defined as
the spontaneous recurrence of itchy wheals and/
or angioedema that are present for > 6 weeks in the ab-
sence of any apparent causes (1). CSU generally has a
prolonged duration of 1 to 5 years and exerts a profound
impact on the patients’ quality of life. The prevalence
of CSU is approximately 1.8% of the adult population
(2). A subset of CSU is considered to be an autoimmune
disease. Circulating autoantibodies including anti-IgE,
anti-FcɛRI, anti-thyroglobulin (TG) or anti-thyroid per-
oxidase (TPO) have been found in patients with CSU.
However, these autoantibodies are not CSU-specific
and therefore, cannot serve as biomarkers reflecting
disease severity and treatment responses. A number of
parameters have been reported to be increased within
the sera or plasma of patients with CSU, but few have
been generally confirmed as being specifically related to
SIGNIFICANCE
Currently, there exist no generally accepted objective bio-
markers for chronic spontaneous urticaria. Therefore, the
identification of new categories of biomarkers for chronic
spontaneous urticaria are urgently needed. To the best of
our knowledge, no published information is available regar-
ding serum miRNA as related to chronic spontaneous urti-
caria. In this study, we provide new and important findings
which show that serum expression of miR-125a-5p and
CCL17 are significantly upregulated in patients with active
chronic spontaneous urticaria and significantly decreased
in the remission phase. Moreover, a further upregulation in
serum miR-125a-5p expression was observed in refractory
chronic spontaneous urticaria cases. These results high-
light the significance of miR-125a-5p and CCL17 as poten-
tial serum biomarkers for chronic spontaneous urticaria.
CSU (3). Accordingly, there is a lack of objective and
specific biomarkers for CSU and the identification of
such biomarkers is urgently needed for this condition.
MicroRNAs (miRNAs) are endogenous ~22nt non-
coding RNA (ncRNA) molecules that decrease targeted
mRNA levels and/or reduce expression of their cog-
nate target proteins. They can accomplish these effects
through a number of different mechanisms including
RNA degradation, induced decapping/deadenylation,
altered cap protein binding, reduced ribosome occupancy,
and/or sequestration of mRNA from translational machi-
nery. MiRNAs, either alone or in combination with other
known biomarkers, have been used as diagnostic tools
in many studies (4). As secreted miRNAs remain stable
in body fluids, they are more readily available for assay
and less invasive than biopsies. These advantages make
them a very appealing diagnostic instrument.
Th2-mediated immune pathways induce mast cell ac-
tivation and degranulation via IgE antibody production
and its binding to the Fcε receptor (FcεR) (5). Th17 cells
show both inhibitory and stimulatory effects on antibody
production by mast cells (6). Of particular relevance to the
current study are the recent findings revealing that Th2/
Th17 cytokines, transcription factors and Th2 chemokines
are upregulated or elevated in CSU patients’ skin lesions,
plasma and serum, respectively (7–10). Accordingly, Th2
and Th17 pathways may be involved in the pathogenesis
of CSU, and CCL17 and IL-17 can serve as serum mar-
kers of Th2 and Th17 inflammation, respectively.
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2019 Acta Dermato-Venereologica.
doi: 10.2340/00015555-3149
Acta Derm Venereol 2019; 99: 571–578