Low and high IgE is linked to improvement and worsening of
chronic urticaria during pregnancy, respectively
Kocatürk E, Thomsen SF, Al-Ahmad M, Gimenez-Arnau A, Conlon N, Savk E,
Criado RF, Danilycheva I, Fomina D, Khoshkhui M, Gelincik A,
Degirmentepe EN, Demir S, Ensina LF, Kasperska-Zajac A, Rudenko M, Bauer
A, Medina I, Maurer M.
1 Urticaria Center of Reference and Excellence (UCARE), Dept. of
Dermatology, Koç University School of Medicine, Istanbul, Turkey
ekocaturk@ku.edu.tr
2 Urticaria Center of Reference and Excellence (UCARE), Center of
Reference and Excellence (UCARE), Department of Dermatology, Bispebjerg
Hospital, Copenhagen, Denmark simonfrancisthomsen@gmail.com
3 Urticaria Center of Reference and Excellence (UCARE), Microbiology
Department, Faculty of Medicine, Kuwait University, Safat, Kuwait
monaalahmad@yahoo.com
4 Urticaria Center of Reference and Excellence (UCARE), Department of
Dermatology, Hospital del Mar, IMIM, Universitat Autònoma, Barcelona,
Spain anamariagimenezarnau@gmail.com
5 Urticaria Center of Reference and Excellence (UCARE), Dermatology, and
Immunology, St James’s Hospital, Dublin, Ireland
conlonn1@tcd.ie
6 Aydın Adnan Menderes University, Aydın, Turkey esavk@adu.edu.tr
7 Urticaria Center of Reference and Excellence (UCARE), Faculdade de
Medicina do ABC (FMABC), Santo André, Brazil roberta.criado@fmabc.br
8 Urticaria Center of Reference and Excellence (UCARE), NRC Institute of
Immunology FMBA of Russia, Moscow, Russia ivdanilycheva@mail.ru
9 Urticaria Center of Reference and Excellence (UCARE), First Moscow
State Medical University, Moscow Center of Allergy and Immunology ,
Clinical Hospital 52 , Ministry of Moscow Healthcare, Moscow, Russia
daria.s.fomina@gmail.com
10 Urticaria Center of Reference and Excellence (UCARE), Allergy
Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Khoshkhuim@mums.ac.ir
11 Urticaria Center of Reference and Excellence (UCARE), Istanbul
Faculty of Medicine Istanbul University, Istanbul, Turkey
gelincikasli@hotmail.com
12 Urticaria Center of Reference and Excellence (UCARE), Okmeydani
Training and Research Hospital, Istanbul, Turkey ecenuryksel@gmail.com
13 Urticaria Center of Reference and Excellence (UCARE), Istanbul
Faculty of Medicine Istanbul University, Istanbul, Turkey
ERTANSEMRA@yahoo.com
14 Urticaria Center of Reference and Excellence (UCARE), Federal
University of São Paulo, Sao Paulo, Brazil 100alergia@gmail.com
15 Urticaria Center of Reference and Excellence (UCARE), European Center
for Diagnosis and Treatment of Urticaria (GA2LEN UCARE Network) Medical
University of Silesia in Katowice, Poland alakasperska@gmail.com
16 Urticaria Center of Reference and Excellence (UCARE), The London
Allergy & Immunology Centre, London, United Kingdom
consultation@ukallergy.com
17 Urticaria Center of Reference and Excellence (UCARE), Department of
Dermatology, University Allergy Center, University Hospital Carl Gustav
Carus, Technical University Dresden, Germany.
Andrea.Bauer@uniklinikum-dresden.de
18 Urticaria Center of Reference and Excellence (UCARE), the Centro
Médico Vitae, Buenos Aires, Argentina irisvmedina@gmail.com
19 Urticaria Center of Reference and Excellence (UCARE), Dermatological
Allergology, Allergie-Centrum-Charité, Dept. of Dermatology and Allergy,
Charité – Universitätsmedizin Berlin, Germany marcus.maurer@charite.de
Dear Editor,
PREG-CU, the recent study on pregnancy and chronic urticaria (CU) by the
Urticaria Centers of Reference and Excellence (UCAREs), showed that CU
improves in half (51.1%) of patients during pregnancy, whereas 28.9%
and 20% of patients, respectively, experienced worsening and no change.
Low disease activity, no angioedema, and no treatment before pregnancy
were risk factors for worsening during pregnancy (1).
We hypothesized that patients with chronic spontaneous urticaria (CSU)
that worsens during pregnancy are more likely to have type I autoimmune
CSU, also called autoallergic CSU. We also hypothesized that patients
who improve during pregnancy are more likely to have type IIb autoimmune
CSU (2). This hypothesis is supported by the immunological changes
observed during pregnancy, i.e., decreased Th1 and Th17 immunity and a
switch to a Th2-type cytokine profile (3).
To test this hypothesis, we retrieved total IgE levels of CSU patients
who gave consent to be included in the PREG-CU study (1). Elevated IgE
levels have been reported to be linked to autoallergic CSU, whereas low
IgE is a marker of type IIb autoimmune CSU (4).
Total IgE blood levels were available for 115 of the 218 CSU patients
not treated with omalizumab enrolled in PREG-CU. The median IgE level
was 106 (range: 3-1664 IU/mL), more than half of patients (51.3%) had
elevated IgE (≥100 IU/mL), and 17.4% had low IgE (<40 IU/mL).
Most patients with mild disease (51%) or moderate disease (61%), but
only one in four patients with severe disease (26%) had elevated IgE
levels (≥100 IU/mL). IgE levels were lower in patients with severe
disease (68 IU/mL) vs mild (112 IU/mL; p=0.009) or moderate disease (128
IU/mL; p=0.018), and low IgE levels (<40 IU/mL) were more
frequent in patients with severe than mild disease (36.8 vs 11.6%;
p=0.034).
CSU patients who got worse during pregnancy had higher IgE levels (154
vs. 82.2 IU/mL; p=0.033) and numerically higher rates of elevated IgE
(57.5 vs. 46%) compared to patients who got better during pregnancy. In
contrast, patients who improved during pregnancy more often had low IgE
levels than patients who deteriorated (22 vs. 12.5%), but this was not
statistically significant. One in three of our patients (34.9%) had
elevated anti-TPO, another marker of type IIb autoimmune CSU, but this
was not linked to improvement during pregnancy.
Worsening of CSU during pregnancy in patients with high IgE levels may
be explained, in part, by the role that IgE and Th2 immunity play in the
pathogenesis of their CSU. High IgE, in CSU, has been linked, in some
studies, to autoallergy, characterized by the presence of IgE
autoantibodies (5). Pregnancy skews immunity towards Th2 responses and
patients with Th2-driven diseases, including allergies, often experience
worsening of their disease during pregnancy (3).
Improvement of CSU during pregnancy in patients with low IgE may point
to a role of Th1 and Th17 cytokines in the pathogenesis of their
disease. Low IgE is a type IIb autoimmune CSU marker, which is linked to
Th1 and Th17 autoimmunity (6). Pregnancy decreases Th1/Th17 immunity,
and patients with TH1/TH17-driven autoimmune diseases often experience
improvement during pregnancy (3). Our finding that elevated
IgG-anti-TPO, another marker of type IIb autoimmune CSU, is not linked
to CSU improvement during pregnancy remains unexplained. Many CSU
patients with IgG-anti-TPO also have IgE-anti-TPO and vice versa, which
could point to both autoallergic and autoimmune drivers of their CSU.
Better biomarkers are needed to identify which patients have
autoallergic CSU, autoimmune CSU, both or none of these.
Our findings support the notion that CSU is a heterogeneous disease,
with at least two endotypes, i.e., autoallergic and autoimmune. Further
studies are needed to better characterize the course of disease during
and after pregnancy, in patients with autoallergic CSU and with
autoimmune CSU. IgE levels may help to predict which CSU patients get
worse and which improve when they get pregnant.