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CLINICAL REPORT
Increase in Vitamin D but not Regulatory T Cells following
Ultraviolet B Phototherapy of Patients with Atopic Dermatitis
Stine SIMONSEN 1 , Charlotte Menné BONEFELD 2 , Jacob Pontoppidan THYSSEN 1 , Carsten GEISLER 2 and Lone SKOV 1
Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, 2 Department of Immunology
and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
1
This study investigated serum 25-hydroxyvitamin D
(25(OH)D) concentrations and circulating regulato-
ry T cells in patients with atopic dermatitis receiving
narrow-band ultraviolet B (nbUVB) phototherapy.
Thirty adult patients with atopic dermatitis were inclu-
ded. Blood samples were collected at baseline and at
weeks 2 and 4 of nbUVB phototherapy. Skin biopsies
were taken at baseline and at week 4. Serum 25(OH)
D concentrations increased significantly following
nbUVB phototherapy (estimate of change from base-
line to week 2: 32.00 nmol/l, confidence interval (CI)
20.48–43.52, p < 0.0001, n = 25; and from baseline to
week 4: 50.30 nmol/l, CI 37.28–63.33, p < 0.0001,
n = 18). This increase was independent of the filaggrin
gene loss-of-function mutation status. Flow cytometry
showed no significant change in regulatory T cells or
cytokine profiles of T cells in blood. Real-time quanti-
tative PCR showed no change in skin cytokine levels.
In conclusion, nbUVB phototherapy was associated
with increased serum 25(OH)D concentrations, but
not changes in circulating regulatory T cells in patients
with atopic dermatitis.
Key words: nbUVB phototherapy; atopic dermatitis; 25-hydroxy
vitamin D; regulatory T cells, filaggrin.
Accepted Sep 23, 2018; E-published Sep 24, 2018
Acta Derm Venereol 2019; 99: 139–145.
Corr: Stine Simonsen, Department of Dermatology and Allergy, Herlev
and Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-
2900 Hellerup, Denmark. E-mail: [email protected]
N
arrow-band ultraviolet B (nbUVB) phototherapy is
an established treatment for atopic dermatitis (AD)
(1). AD is a complex trait characterized by a dysfunctio-
nal skin barrier and a pathological immune polarization.
Although different endotypes may exist, AD is characte-
rized by a strong activation of T H 2 immune responses in
lesional and non-lesional skin, with some contribution
from the T H 22, T H 17/IL-23, and T H 1 cytokine pathways
(2). Regulatory T cells are pivotal for maintenance of
self-tolerance and probably also for the regulation of
unwanted immune activation, such as in atopy (3). How
ever, the role of regulatory T cells in the pathogenesis
of AD is not fully understood. Several studies have
suggested that patients with AD have increased levels
of circulating regulatory T cells compared with healthy
controls, although the data are conflicting (4–8). Vitamin
D is central for immune function (9). Notably, vitamin
SIGNIFICANCE
Vitamin D synthesis is induced by ultraviolet B irradiation
of the skin and may have a beneficial effect on the immune
system in patients with atopic dermatitis. We measured
changes in vitamin D levels and immunological markers
in patients with atopic dermatitis receiving ultraviolet B
phototherapy. Following ultraviolet B phototherapy, vita-
min D levels were increased, as expected, but no changes
were found in the immune system. Furthermore, ultraviolet
B phototherapy induced equal increases in the vitamin D
levels in patients with atopic dermatitis with and without a
mutation that causes a defective skin barrier.
D levels may be associated with the risk and severity of
AD, and a few small studies have shown that vitamin D
supplementation may reduce the clinical severity of AD
(10). A recent study has investigated circulating regula-
tory T cells and serum 25-hydroxyvitamin D (25(OH)D)
concentration in a group of patients with different in-
flammatory skin diseases who were undergoing nbUVB
phototherapy (11). The authors showed that the numbers
of regulatory T cells increased mainly in the first 14 days
of nbUVB phototherapy, and that there was a correlation
between this increase and an increase in serum 25(OH)D
concentration.
Loss-of-function mutations in the filaggrin gene, FLG,
result in a complete or partial lack of monomeric filag-
grin in the epidermis, and are a strong risk factor for AD
(12). Filaggrin is metabolized to amino acids and their
derivatives, which constitute a major part of the natural
moisturizing factors in the upper layers of the stratum
corneum. One important metabolite is trans-urocanic
acid (trans-UCA), a key UVB photon-absorbing chro-
mophore of the epidermis (13). In vitro and animal stu-
dies have suggested that decreased levels of trans-UCA
result in increased keratinocyte UVB photosensitivity
(14–18). A meta-analysis of cross-sectional studies has
shown that subjects with FLG loss-of-function mutations
have a 10% higher concentration of serum 25(OH)D
concentration than wild-type (WT) subjects (19). Based
on these observations, one may hypothesize that FLG
loss-of-function mutations cause increased epidermal
penetration of UVB photons and thereby increased
25(OH)D synthesis. This study investigated changes in
serum 25(OH)D concentration and circulating regulatory
T cells in the early stage of nbUVB phototherapy in a
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2019 Acta Dermato-Venereologica.
doi: 10.2340/00015555-3050
Acta Derm Venereol 2019; 99: 139–145