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Narrow-band ultraviolet B treatment boosts serum 25-hydroxyvitamin D in patients with psoriasis on oral vitamin D supplementation

Abstract

A course of treatment with narrow-band ultraviolet B (NB-UVB) improves psoriasis and increases serum 25-hydroxyvitamin D (25(OH)D). In this study 12 patients with psoriasis who were supplemented with oral cholecalciferol, 20 µg daily, were given a course of NB-UVB and their response measured. At baseline, serum 25(OH)D was 74.14 ± 22.9 nmol/l. At the 9th exposure to NB-UVB 25(OH)D had increased by 13.2 nmol/l (95% confidence interval (95% CI) 7.2-18.4) and at the 18th exposure by 49.4 nmol/l (95% CI 35.9-64.6) above baseline. Psoriasis Area Severity Index score improved from 8.7 ± 3.5 to 4.5 ± 2.0 (p < 0.001). At baseline, psoriasis lesions showed low vitamin D metabolizing enzyme (CYP27A1, CYP27B1) and high human β-defensin-2 mRNA expression levels compared with those of the healthy subjects. In conclusion, NB-UVB treatment significantly increases serum 25(OH)D in patients with psoriasis who are taking oral vitamin D supplementation, and the concentrations remain far from the toxicity level. Healing psoriasis lesions show similar mRNA expression of vitamin D metabolizing enzymes, but higher antimicrobial peptide levels than NB-UVB-treated skin in healthy subjects.

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Narrow-band ultraviolet B treatment boosts serum 25-hydroxyvitamin D in patients with psoriasis on oral vitamin D supplementation

Author: Ala-Houhala, Meri,Karppinen, Toni,Vähävihu, Katja,Kautiainen, Hannu,Dombrowski, Yvonne,Snellman, Erna,Schauber, Jürgen,Reunala, Timo
Year: 2014
Source: https://trepo.tuni.fi/bitstream/10024/99794/1/narrow-band_ultraviolent_2014.pdf
Ac a De m Vene eol 94
INVESTIGATIVE REPORT
Ac a De m Vene eol 2014; 94: 146–151
© 2014 The Au ho s. doi: 10.2340/00015555-1685
Jou nal Compila ion © 2014 Ac a De ma o-Vene eologica. ISSN 0001-5555
A cou se o ea men wi h na ow-band ul a iole
B (NB-UVB) imp o es pso iasis and inc eases se um
25-hyd oxy i amin D (25(OH)D). In his s udy 12 pa-
ien s wi h pso iasis who we e supplemen ed wi h o al
cholecalci e ol, 20 µg daily, we e gi en a cou se o NB-
UVB and hei esponse measu ed. A baseline, se um
25(OH)D was 74.14 ± 22.9 nmol/l. A he 9 h exposu e o
NB-UVB 25(OH)D had inc eased by 13.2 nmol/l (95%
con idence in e al (95% CI) 7.2–18.4) and a he 18 h
exposu e by 49.4 nmol/l (95% CI 35.9–64.6) abo e base-
line. Pso iasis A ea Se e i y Index sco e imp o ed om
8.7 ± 3.5 o 4.5 ± 2.0 (p < 0.001). A baseline, pso iasis le-
sions showed low i amin D me abolizing enzyme (CY-
P27A1, CYP27B1) and high human β-de ensin-2 mRNA
exp ession le els compa ed wi h hose o he heal hy
subjec s. In conclusion, NB-UVB ea men signi ican ly
inc eases se um 25(OH)D in pa ien s wi h pso iasis who
a e aking o al i amin D supplemen a ion, and he con-
cen a ions emain a om he oxici y le el. Healing
pso iasis lesions show simila mRNA exp ession o i a-
min D me abolizing enzymes, bu highe an imic obial
pep ide le els han NB-UVB- ea ed skin in heal hy sub-
jec s. Key wo ds: pso iasis; ul a iole B adia ion; i amin
D; CYP27A1; CYP27B1; ca helicidin; human β-de ensin.
Accep ed Ap 29, 2013; Epub ahead o p in Aug 27, 2013
Ac a De m Vene eol 2014; 94: 146–151.
Timo Reunala, Depa men o De ma ology, Tampe e
Uni e si y Hospi al, PO Box 2000, FIN-33521, Tampe e,
Finland. E-mail: [email p o ec ed]
Vi amin D insu iciency is common in Eu ope and No h
Ame ica, especially du ing he win e when i amin D
syn hesis induced by sunligh is ze o (1, 2). The desi able
concen a ion o se um 25-hyd oxy i amin D (25(OH)
D), which is he bes indica o o i amin D s a us, is
s ill unde deba e. A concen a ion below 75 nmol/l (30
ng/ml) is conside ed o be insu icien o bone ac u e
p e en ion (3). In addi ion o os eopo osis, low se um
25(OH)D concen a ion has ecen ly been associa ed wi h
isk o colo ec al cance and ca dio ascula disease (4,
5). Vi amin D is also known o a ec skin in lamma ion
and inna e o adap i e immune esponses (6, 7).
Recen s udies sugges ha i amin D insu iciency is
also common in pa ien s wi h pso iasis (8–10). Gisondi
e al. (8) ound ha , in I aly in win e , se um 25(OH)D
was below 50 nmol/l in 81% o pa ien s wi h pso iasis
compa ed wi h 30% o heal hy con ols. They also sho-
wed ha i amin D insu iciency was associa ed wi h
pso iasis independen ly o age, sex and body mass index
(BMI). Romaní e al. (10) concluded ha he insu i-
ciency was also common in pa ien s wi h pso iasis and
con ols in Spain, bu in hei s udy ca e ully ma ched
con ols had a highe insu iciency a e han pa ien s
wi h pso iasis.
Na ow-band UVB (NB-UVB) pho o he apy, a wi-
dely used e ec i e ea men o pso iasis (11), supp es-
ses in e e on-gamma (IFN-γ) and in e leukin (IL)-17
signalling pa hways o esol e pso ia ic in lamma ion
(12). NB-UVB ligh emi ing a 311–313 nm is also
capable o ac i a ing i amin D syn hesis in cul u ed
ke a inocy es (13). Mo eo e , se e al s udies ha e
shown ha , in addi ion o healing o pso iasis, NB-
UVB ea men signi ican ly inc eases se um 25(OH)D
(14–17), and his inc ease co ela es wi h he ac i a ion
o ci cula ing egula o y T cells (18).
In e es ingly, he exp ession o ca helicidin, which
is one o he mos impo an an imic obial pep ides in
human skin, is dependen on 1,25-dihyd oxy i amin
D (1,25(OH)
2
D) and is igge ed by UVB-induced i-
amin D me abolism (6, 19). Ca helidicin and ano he
inducible cu aneous an imic obial pep ide, human
β-de ensin-2 (HBD2), can ac as immune- egula ing
e ec o s o “ala mins” and link adap i e and inna e
immune esponses (20). In addi ion, hese an imic o-
bial pep ides seem o ha e a ole in he con ol o skin
in lamma ion in pso iasis (21, 22).
The p esen s udy examined whe he NB-UVB ea -
men can inc ease se um 25(OH)D in pa ien s wi h pso-
iasis who a e al eady supplemen ed wi h o al i amin
D. In addi ion, we in es iga ed he e ec s o NB-UVB
exposu e on cu aneous mRNA exp ession o i amin
D-me abolizing enzymes and an imic obial pep ides.
Na ow-band Ul a iole B T ea men Boos s Se um 25-hyd oxy i amin
D in Pa ien s wi h Pso iasis on O al Vi amin D Supplemen a ion
Me i J. ALA-HOUHALA1,2, Toni T. KARPPINEN3, Ka ja VäHäVIHU4, Hannu KAUTIAINEN5, Y onne DOMBROwSKI6, E na
SNELLMAN3, Jü gen SCHAUBER6 and Timo REUNALA1,2
1Depa men o De ma ology, Tampe e Uni e si y Hospi al, 2Medical School, Uni e si y o Tampe e, Tampe e, Depa men s o De ma ology, 3Päijä -Häme
Cen al Hospi al, Lah i,4Kan a-Häme Cen al Hospi al, Hämeenlinna, 5Uni s o P ima y Heal h Ca e, Helsinki and Tu ku Uni e si y Hospi als, and Depa -
men o Gene al P ac ice, Uni e si y o Helsinki, Finland, and 6Depa men o De ma ology and Alle gy, Ludwig-Maximilian-Uni e si y, Munich, Ge many
147
Na ow-band UVB and i amin D in pso iasis
METHODS
Pa ien s wi h pso iasis and heal hy subjec s
A o al o 12 pa ien s wi h pso iasis (mean age 42.8 yea s; Table
I) pa icipa ed in he s udy. Fou pa ien s had also pso ia ic
a h i is, bu none o hem ecei ed any sys emic d ug ea men
because hei a h i is was no ac i e du ing he s udy. Inclu-
sion c i e ia we e no pho o he apy, sola ium o sunny holidays
du ing he 2 p eceding mon hs. Be o e he NB-UVB cou se he
pa ien s had used cholecalci e ol 20 µg (800 IU) daily o a
mean o 3.3 mon hs (Table I). Fi een nu ses and o he hospi al
employees (mean age 46.1 yea s; Table I) olun ee ed as con-
ols in he s udy. These subjec s had used o al cholecalci e ol
o a mean o 3.4 mon hs (Table I). The pa ien s wi h pso iasis
and he heal hy subjec s con inued o use o al cholecalci e ol
du ing he NB-UVB cou se and subsequen o i .
The s udy p o ocol was app o ed by he e hics commi ee
o Tampe e Uni e si y Hospi al and all subjec s ga e hei
in o med consen o pa icipa e. The s udy p o ocol ollowed
he p inciples o he Decla a ion o Helsinki.
Na ow-band UVB exposu e
The s udy was pe o med in win e om Decembe 2011 o Ap il
2012 in o de o exclude he e ec o he sun. The s udy subjec s
ecei ed NB-UVB exposu e 3 imes a week on he whole body
a ea wi h a Waldmann UV 7001 cabin equipped wi h 40 TL01
ubes (Schulze & Böhm, B ühl, Ge many). The i s NB-UVB
dose was 0.19 J/cm2 (1.11 s anda d e y hema dose (SED)) and i
was g adually inc eased each ime, acco ding o a ixed p o ocol,
up o 9 exposu es, i.e. o 0.97 J/cm2 (5.70 SED). I he subjec s
expe ienced mild i ching o e y hema, he nex NB-UVB dose
was ei he no inc eased o was educed. This was he case in
6 pa ien s wi h pso iasis and 8 heal hy subjec s. The ea e , he
NB-UVB ea men was gi en only o pa ien s wi h pso iasis un il
he ash was almos o o ally clea ed. This ook a mean o 20.5
( ange 11–31) NB-UVB exposu es. Clinical imp o emen was
measu ed wi h he
Pso iasis A ea Se e i y Index
(PASI) sco e.
The mean cumula i e dose o NB-UVB gi en o he 12 pa ien s
wi h pso iasis du ing 9 exposu es was 4.49 ± 0.44 J/cm2 and o he
9 pa ien s du ing 18 exposu es 15.63 ± 1.67 J/cm2. These doses a e
equi alen o 26.4 ± 2.6 SED and o 91.9 ± 9.8 SED, espec i ely.
One SED is equi alen o 10 mJ/cm2 Commission In e na ionale de
l’Eclai age (CIE) e y hema-weigh ed i adiance. In he 15 heal hy
subjec s he mean cumula i e dose o 9 NB-UVB exposu es was
4.37 ± 0.55 J/cm2, which is equi alen o 25.7 ± 3.2 SED. The cu-
mula i e NB-UVB doses gi en up o 9 exposu es o he pa ien s
wi h pso iasis and heal hy subjec s did no di e (p = 0.57).
Measu emen o se um 25-hyd oxy i amin D concen a ions
Blood samples o se um 25(OH)D measu emen s we e aken
a baseline, and a 9 h and 18 h NB-UVB exposu es. Follow-up
samples we e aken one mon h a e he NB-UVB cou se. The
samples we e p o ec ed om ligh , cen i uged and hen s o ed
a –70ºC. Se um 25(OH)D concen a ion was analysed in du-
plica es using adioimmunoassay (Immunodiagnos ic Sys ems,
Boldon, UK), as desc ibed p e iously (23).
Skin biopsies and quan i a i e eal- ime PCR
Punch biopsies we e aken om skin lesions o 12 pa ien s wi h
pso iasis (8 om he bu ocks, 2 om elbows, and 2 om lowe
back) and om he bu ocks o 13 heal hy subjec s a baseline
and a he 9 h NB-UVB exposu e. The biopsies we e immedia ely
ozen and s o ed a –70ºC. To al RNA om biopsies was iso-
la ed using TRIsu e Reagen (Bioline, Luckenwalde, Ge many)
and 1 µg o RNA was e e se- ansc ibed wi h High Capaci y
cDNA Re e se T ansc ip ion Ki (Applied Biosys ems, Fos e
Ci y, CA, USA) o cDNA. The mRNA exp ession le els o
CYP27A1 and CYP27B1 enzymes, and an imic obial pep ides
ca helicidin and HBD2 we e e alua ed using a Ligh Cycle ® 2.0
sys em and he co esponding human Uni e sal P obe Lib a y
Se (Roche), as desc ibed p e iously (15).
S a is ical analysis
S a is ical compa ison be ween he g oups was pe o med by
S uden ’s - es , pe mu a ion es o χ2 es , when app op ia e.
The changes wi hin pa ien s wi h pso iasis and heal hy sub-
jec s we e analysed by applying a pe mu a ion es o ela ed
samples. Repea ed measu es we e analysed using gene alizing
es ima ing equa ion models wi h he uns uc u ed co ela ion
s uc u e using boo s ap- ype s anda d e o .
RESULTS
Se um 25(OH)D concen a ions a baseline, du ing and
a e NB-UVB cou se
A baseline, se um 25(OH)D concen a ion was
74.14 ± 22.9 nmol/l (mean ± SD) in he 12 pa ien s
wi h pso iasis and 74.30 ± 14.8 nmol/ in he 15 heal hy
subjec s. A 9
h
NB-UVB exposu e se um 25(OH)D had
inc eased by 13.2 nmol/l (95% CI 7.2–24.9, p = 0.0029)
in he pa ien s wi h pso iasis and by 17.0 nmol/l (95%
CI 6.7–21.0, p < 0.001) in he heal hy subjec s (Fig. 1,
Table II).
A 18
h
NB-UVB exposu e 25(OH)D had inc eased
by 49.4 nmol/l (95% CI 35.9–64.6, p = 0.0039) in he 9
pa ien s wi h pso iasis (Table II). PASI sco e imp o ed
in he pa ien s wi h pso iasis om 8.7 ( ange 4.0–16.2)
a baseline o 6.4 ( ange 2.1–12.8) a 9
h
and o 4.5 ( ange
1.1–8.2) a 18
h
exposu e (p < 0.001; Table II).
One mon h a e NB-UVB exposu e, se um 25(OH)D
was s ill inc eased om baseline by 29.9 nmol/l (95%
CI 13.6–49.0; p = 0.0078) in he 8 pa ien s wi h pso iasis
and by 17.5 nmol/l (95% CI 10.1–24.9; p < 0.001) in he
15 heal hy subjec s (Table II).
An imic obial pep ide and enzyme mRNA exp ession in
skin biopsy specimens
A baseline, he mRNA exp ession le els o CYP27A1
and CYP27B1 we e signi ican ly lowe (p < 0.001) in
Table I. Demog aphy and use o o al cholecalci e ol be o e na ow-
band ul a iole B (NB-UVB) cou se in 12 pa ien s wi h pso iasis
and 15 heal hy subjec s
Pso iasis
pa ien s
Heal hy
subjec s p- alue
Male/ emale, n7/5 1/14 0.008
Age, yea s, mean ± SD 42.8 ± 14 46.1 ± 11 0.47
Body mass index, kg/m2, mean ± SD 29.6 ± 5.4 23.4 ± 3.8 0.002
Fi zpa ick skin ype II/III/IV, n3/6/3 3/10/2 0.66
O al cholecalci e ol, 20 µg daily be o e
NB-UVB cou se, mon hs, mean ( ange) 3.3 (1–24) 3.4 (1–24) 0.75
SD: s anda d de ia ion.
Ac a De m Vene eol 94
148 M. J. Ala-Houhala e al.
he pa ien s wi h pso iasis han in heal hy subjec s (Fig.
2A and B, Table III). A baseline ca helicidin mRNA
exp ession le els we e simila in he pso iasis lesions
and in he no mal skin o heal hy subjec s, whe eas
HBD2 mRNA le els we e signi ican ly (p < 0.001)
highe in he pso iasis lesions (Fig. 2C, Table III).
NB-UVB exposu e did no change CYP27A1,
CYP27B1 and ca helidicin mRNA exp ession le els in
he pa ien s wi h pso iasis, bu a signi ican (p = 0.002)
dec ease was seen in he HBD2 mRNA exp ession le el
(Fig. 2 and Table III). In he heal hy subjec s NB-UVB
exposu e signi ican ly dec eased CYP27A1, CYP27B1
and ca helidicin mRNA exp ession le els, while HBD2
inc eased sligh ly (Fig. 2, Table III).
DISCUSSION
Se e al ecen s udies ha e demons a ed ha NB-UVB,
a widely used ea men o pso iasis (11), signi ican ly
imp o es se um 25(OH)D concen a ions, especially
du ing he win e (10, 14–17). The numbe o NB-UVB
exposu es gi en in hese pso iasis s udies a ied om 15
o 27 and he inc ease in se um 25(OH)D anged om
66% o 163% (Table IV). In con as o hese p e ious
s udies, he p esen pa ien s wi h pso iasis we e addi io-
nally supplemen ed wi h o al 20 µg o cholecalci e ol
daily o a mean o 3.3 mon hs be o e en y in o he ial.
Due o his p e- ea men hei mean se um 25(OH)D
was 74 nmol/l a baseline, which is wice as high as in
ou p e ious s udy (14). Ne e heless, UVB ea men
u he inc eased se um 25(OH)D, by 17% a he 9
h
and by 58% a he 18
h
NB-UVB exposu e. Al hough
he BMI was signi ican ly lowe in he heal hy subjec s
han in he pa ien s wi h pso iasis, he baseline 25(OH)D
concen a ion and he inc ease a 9
h
NB-UVB exposu e
was o app oxima ely he same magni ude. This inding
is somewha unexpec ed because obese subjec s a e mo e
p one o i amin D insu iciency due o he deposi ion o
i amin D p ecu so s in a issue (2, 24). In a ecen s udy
(25) in which subjec s we e supplemen ed wi h 15 µg o al
cholecalci e ol daily, BMI in olde , bu no in younge ,
adul s was shown o be nega i ely associa ed wi h he
change in se um 25(OH)D. These esul s indica e ha
BMI is impo an when pe o ming i amin D s udies,
and i amin D insu iciency epo ed in some pso iasis
s udies could be a ibu ed o obesi y and como bidi ies
associa ed wi h se e e pso iasis. The limi a ion o he
p esen s udy is ha he pa ien s wi h pso iasis and he
heal hy subjec s we e no ma ched o BMI. Howe e ,
he simila and signi ican inc eases in se um 25(OH)
D le els in bo h g oups who we e con inuously supple-
men ed wi h a a he high dose o o al i amin D indica e
ha NB-UVB exposu e is an e icien way o imp o e
i amin D balance. In ag eemen wi h his, 2 ecen
s udies in heal hy subjec s ha e documen ed he supe i-
o i y o NB-UVB exposu e o e o al supplemen a ion o
cholecalci e ol, 20 µg and 40 µg daily, o imp o e se um
25(OH)D concen a ion (23, 26).
In he p esen s udy he mean inc ease in se um
25(OH)D a he 18
h
NB-UVB exposu e was 58%
and he highes indi idual concen a ion measu ed
155 nmol/l. O e all, he inc ease obse ed was no as
ma ked as in p e ious pso iasis s udies (Table IV). This
is no unexpec ed, because i appea s o be e iden ha
he lowe he s a ing 25(OH)D concen a ion he highe
Table II. Na ow-band UVB (NB-UVB) doses, se um 25-hyd oxy i amin D (25(OH)D) concen a ions and Pso iasis A ea Se e i y Index
(PASI) sco es in 12 pa ien s wi h pso iasis and 15 heal hy subjec s
A baseline
A 9 h NB-UVB
exposu e
A 18 h NB-UVB
exposu e
1 mon h a e
NB-UVB cou se
Pa ien s wi h pso iasis, n
To al NB-UVB dose, J/cm2, mean ± SD
25(OH)D; nmol/l, mean ± SD
PASI sco e, mean ± SD
12
–
74.1 ± 22.9
8.7 ± ±3.5
12
4.5 ± 0.4
87.3 ± ± 16.0
6.4 ± 3.1
9
15.6 ± 1.7
117.3 ± 28.9
4.5 ± 2.0
8
–
115.0 ± 26.5
–
Heal hy subjec s, n
To al NB-UVB dose, J/cm2
25(OH)D, nmol/l, mean ± SD
15
–
74.3 ± 14.8
15
4.37 ± 0.6
91.3 ± 17.1
– 15
–
88.3 ± 19.9
Fig. 1. Se um 25-hyd oxy i amin D (25(OH)D) concen a ions be o e and a
9 h (a e ) na ow-band ul a iole B (NB-UVB) exposu e in 12 pa ien s wi h
pso iasis and 15 heal hy subjec s. The pa ien s wi h pso iasis and heal hy
subjec s ecei ed o al cholecalci e ol, 20 µg daily. The inc ease is signi ican
in he pa ien s wi h pso iasis (p = 0.003) and heal hy subjec s (p < 0.001).
L
Ac a De m Vene eol 94
149
Na ow-band UVB and i amin D in pso iasis
he esponse o UVB ea men (27). Mo eo e , he e
is e idence ha du ing UVB exposu e o he skin, bu
no du ing o al supplemen a ion, a nega i e eedback
mechanism con ols i amin D syn hesis o p e en
o e dosing and i amin D oxici y (28). I is no ewo -
hy in his con ex , ha 1 o he p esen pa ien s had an
excep ionally high le el o se um 25(OH)D, i.e.130
nmol/l a baseline and she was he only one o espond
o NB-UVB exposu e wi h dec eased se um 25(OH)D.
In addi ion, al hough he pa ien s and heal hy subjec s
con inued wi h o al cholecalci e ol supplemen a ion,
se um 25(OH)D concen a ions s a ed o dec ease one
mon h a e NB-UVB exposu e. This is in ag eemen
wi h ou p e ious NB-UVB s udies (15, 23) and demon-
s a es ha e en a he high con inuous o al i amin
D supplemen a ion is no su icien o main ain se um
25(OH)D le els achie ed by a sho cou se o NB-UVB
exposu e. I has been epo ed ha NB-UVB exposu e
gi en wice a mon h main ains he le els o 25(OH)
D achie ed in he summe (29). The e o e, a simila
schedule could be applicable o he NB-UVB- ea ed
pa ien s wi h pso iasis du ing he win e in o de o
main ain su icien i amin D.
A p e ious s udy in UVB- ea ed o gan cul u es sho-
wed ha CYP27A1 and CYP27B1 in he ke a inocy es
a e capable o hyd oxyla ing p ecu so s in o he ac i e
o m o i amin D, i.e. 1,25(OH)
2
D (13). Thus, bo h
enzymes could be ega ded as su oga e ma ke s o
i amin D me abolism. In he p esen s udy he exp es-
sion le els o CYP27A1 and CYP27B1 a baseline we e
low in he pso ia ic lesions compa ed wi h heal hy skin
and did no change du ing NB-UVB ea men . A i s ,
he low baseline le el o CYP27B1 in pso iasis lesions
seems di icul o explain. Howe e , he pa ien s wi h
pso iasis we e supplemen ed wi h o al cholecalci e ol,
and i could be ha he me abolism o i amin D in he
pso iasis lesions is a mo e ac i e han in he no mal
skin o heal hy subjec s. Due o his, he low CYP27A1
and CYP27B1 ac i i ies in he pso iasis lesions a
baseline and a e NB-UVB exposu e, and also in he
no mal skin a e NB-UVB exposu e, could be due o a
e y sensi i e na u al eedback con olling mechanism
in cu aneous i amin D syn hesis (6, 7).
An imic obial pep ides seem o ha e a ole in he
pa hogenesis o skin in lamma ion in pso iasis (21, 30).
In ag eemen wi h ou p e ious s udy (15), we ound
in pso iasis lesions a baseline signi ican ly inc eased
mRNA exp ession o HBD2. we could also show ha
epea ed NB-UVB exposu e educed HBD2 exp ession
in healing pso iasis lesions. In con as o HBD2, we
ound no inc eased mRNA exp ession o ca helicidin
in he pso iasis lesions, ei he a baseline o a e NB-
UVB exposu e. This is su p ising wi h ega d o he
indings o ou p e ious s udy (15). The con inuous
Table III. Vi amin D me abolizing enzyme and an imic obial pep ide mRNA exp ession le els in he pso iasis lesions o 12 pa ien s and
no mal skin o 13 heal hy subjec s a baseline and a 9 h na ow-band UVB (NB-UVB) exposu e
Pso iasis
p- alue
Heal hy subjec s
p- alue
Baseline
Mean ± SD
A 9 h NB-UVB
Mean ± SD
Baseline
Mean ± SD
A 9 h NB-UVB
Mean ± SD
CYP27A1 0.16 ± 0.85 0.23 ± 0.13 0.17 1.05 ± 0.34 0.43 ± 0.14 < 0.001
CYP27B1 0.69 ± 0.14 0.60 ± 0.18 0.070 1.04 ± 0.35 0.63 ± 0.18 0.0017
Ca helicidin 1.81 ± 1.51 1.70 ± 1.58 0.88 1.32 ± 0.99 0.12 ± 0.08 < 0.001
Human β-de ensin-2 41,739 ± 65,700 1,497 ± 1,037 0.002 159.65 ± 302.49 471.84 ± 328.71 0.041
Fig. 2. (A) CYP27A1 mRNA, (B) CYP27B1 mRNA and (C) ca helicidin mRNA exp ession le els in skin lesions o pa ien s wi h pso iasis (n = 12) and
no mal skin o heal hy subjec s (n = 13) be o e and a 9 h (a e ) na ow-band ul a iole B (NB-UVB) exposu e. Be o e NB-UVB cou se he CYP27A1
and CYP27B1 le els a e signi ican ly lowe (p < 0.001), bu he ca helidicin le els do no di e (p = 0.34) in he pa ien s wi h pso iasis compa ed wi h he
heal hy subjec s. NB-UVB exposu e did no change CYP27A1 mRNA, CYP27B1 mRNA o ca helidicin mRNA le els in he pa ien s wi h pso iasis (A:
p = 0.17; B: p = 0.070; C: p = 0.88) bu he dec ease is signi ican (A: p < 0.001; B: p = 0.002; C: p < 0.001) in he heal hy subjec s.
Ac a De m Vene eol 94
150 M. J. Ala-Houhala e al.
o al supplemen a ion wi h i amin D be o e he s udy,
wi h possible accumula ion o i amin D p ecu so s and
1,25(OH)
2
D in he pso iasis lesions and ac i a ion o
nega i e eedback mechanisms, could again be a eason
o his inding. O e all, he p esen ca helidicin and
i amin D-me abolizing enzyme gene exp ession esul s
sugges ha he no mal skin o heal hy subjec s eac s
mo e ac i ely o NB-UVB exposu e han he in lamed
skin o pso iasis lesions. I is, howe e , no ewo hy ha
in spi e o hese gene exp ession di e ences he pa ien s
wi h pso iasis and heal hy subjec s showed simila NB-
UVB esponses in he se um 25(OH)D concen a ion.
Knowledge o he isk o i amin D insu iciency is
well-accep ed. In Finland, o example, he e a e ecom-
menda ions o child en and p egnan women o use up
o 10 µg and o elde ly people up o 20 µg daily o o al
i amin D supplemen a ion (31). Mo eo e , i amin D
p oduc s a e ac i ely ma ke ed and olun a y supple-
men a ion especially du ing win e mon hs is now also
common among de ma ological pa ien s. Many pa ien s
wi h pso iasis will ecei e NB-UVB ea men , which is
e ec i e and, in he sho - e m, is conside ed sa e wi h
ega d o isk o skin malignancy (32, 33). The p esen
NB-UVB s udy documen ed ha e en hough he pa-
ien s wi h pso iasis ecei ed o al cholecalci e ol 20 µg
daily hei se um 25(OH)D concen a ions emained a
om 250 nmol/l. Le els below his a e conside ed sa e
wi h ega d o oxici y (34) and, he e o e, we conclude
ha he e is no need o s op olun a y o al i amin D
supplemen a ion whene e pa ien s wi h pso iasis need
o s a NB-UVB ea men . In addi ion, in he p esen
s udy pa ien s wi h pso iasis supplemen ed wi h o al
cholecalci e ol showed a simila signi ican dec ease
in PASI sco e, as did he pa ien s wi h no o al i amin
D supplemen a ion in ou p e ious s udy (15). This
sugges s ha he esponse o NB-UVB ea men in
pso iasis is no dependen on whe he he pa ien is
supplemen ed wi h o al i amin D.
In conclusion, his s udy showed ha , al hough
he pa ien s wi h pso iasis ecei ed con inuous o al
cholecalci e ol supplemen a ion, NB-UVB exposu e
inc eased se um 25(OH)D concen a ion by 58%. In
healing pso iasis lesions NB-UVB ea men did no
al e he exp ession o i amin D-me abolizing enzyme
and ca helidicin mRNA, bu dec eased he exp ession
o HBD2 mRNA.
ACKNOWLEDGEMENTS
This s udy was suppo ed by Na ional G adua e School o
Clinical In es iga ion (M.A-H), and by Compe i i e Resea ch
Funding o he Tampe e Uni e si y Hospi al (G an s 9K104 and
9M089). The au ho s would like o hank nu ses Pi jo Honko and
Tuija Valjakka o p o iding he NB-UVB exposu e in he s udy.
The au ho s decla e no con lic s o in e es .
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