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Journal of Medicine and Life Vol. 13, Issue 4, October-December 2020, pp. 463–468
463
DOI: 10.25122/jml-2020-0015
Vitamin D and Immunoglobulin E Status in Allergic Rhinitis Patients
Compared to Healthy People
Haitham Alnori1*, Fawaz Abdulghani Alassaf2, Mohanad Alfahad3, Mohannad Emad Qazzaz4,
Mahmood Jasim5, Mohammed Najim Abed6
1. Department of Surgery, College of Medicine, University of Mosul, Mosul, Iraq
2. Department of Pharmacology, College of Pharmacy, University of Mosul, Mosul, Iraq
3. Department of Pharmaceutics, College of Pharmacy, University of Mosul, Mosul, Iraq
4. Department of Pharmacognosy and Medicinal Plants, College of Pharmacy, University of Mosul, Mosul, Iraq
5. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, Iraq
6. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, Iraq
* Corresponding Author:
Haitham Alnori,
Department of Surgery, College of Medicine,
University of Mosul,
Mosul Ninavah 00964 Iraq.
Phone: 009647701637724
E-mail: haithamabdnori@uomosul.edu.iq
Received: January 19th, 2020 – Accepted: April 20th, 2020
Abstract
Allergic rhinitis (AR) is a type of inammatory condition that includes a group of symptoms, mainly affecting the nasal mucosa. Nasal
obstruction, sneezing, stuffy or runny nose, in addition to swollen, itchy, red and watery eyes are the most common symptoms of the
disease. These symptoms are triggered as a result of increased inammatory mediators such as histamine and leukotrienes. Studies
have recently shown the role of vitamin D (vit.D) in many allergic and immune conditions, where receptors for the active form of vit.D
(1,25-dihydroxyvitamin D3) have been discovered on the surface of almost all types of inammatory cells. Therefore, the present study
was conducted to explore the level of vit. D in AR patients and its correlation with the severity of the disease. Two groups participated
in the study; the rst group included 49 patients who were diagnosed in a private otolaryngology clinic by the rst author as having
allergic rhinitis (AR group). The second one served as a control group and included 50 apparently healthy volunteers with no history
of AR. The mean level of IgE and vit. D was found to be 326.3 and 10.2 ng/ml in the AR group, respectively, and 30.8 and 23.3 ng/ml
in the control group, respectively. Ninety-three percent of AR patients have shown a deciency in vit. D level, where 56% of this group
showed severe deciency. On the other hand, 34% of the control group has shown an insufcient level of vit. D. Additionally, 64% of
AR patients have shown serum levels of IgE at values ranging between 100-299 ng/ml. Higher serum levels of IgE at values ranging
between 300-599 ng/ml and 600-1000 ng/ml were observed in 25% and 11% of AR patients, respectively. The prevalence of low levels
of vit. D in the AR group was signicantly higher than that in the control group (P < 0.001). Vit. D deciency is signicantly related to
severe AR symptoms and measuring serum vit. D level is recommended in the management plan of this group of patients.
Keywords: Allergic rhinitis, vitamin D and allergic rhinitis, IgE and allergic rhinitis, vitamin D and IgE, vitamin D, IgE and allergic rhinitis.
Introduction
Allergic rhinitis is an inammatory condition of the nasal
mucosa. Typical symptoms include nasal obstruction/ con-
gestion, itching, watery nose, and sneezing [1]. Although
it mainly affects the nose, AR is now considered a com-
ponent in the diseases of the entire respiratory tract. AR
affects about 10-20% of the global population, with around
500 million patients worldwide [2]. However, the preva-
lence of the disease differs between countries and is re-
lated to genetic, geographic, and climate factors and the
types of allergens in a specic region [3]. In Iraq, a study
was conducted by Alsamarai et al. [4] to test the correlation
between AR and asthma in the Iraqi population, based on
evidence that many asthmatic patients also suffer from AR
[5]. The study showed that over 60% of asthmatic patients
suffer from AR, and 6% of the non-asthmatic control popu-
lation from Iraq have AR [4].
Traditionally, AR was classied as seasonal (symp-
toms appearing in a particular season) or perennial (symp-
toms throughout the year). This classication is no longer
employed since some allergens may be seasonal in some
regions and perennial in others, and many patients have
multiple seasonal attacks throughout the year [6]. A more
recent classication is based on symptoms’ duration (inter-
Journal of Medicine and Life Vol. 13, Issue 4, October-December 2020, pp. 463–468
464
mittent and persistent) and severity (mild and moderate to
severe). Intermittent AR is dened as symptoms occurring
for less than four weeks at a time, while in the persistent
class, the patient is suffering for most of the year. Mild
symptoms involve those that do not interfere with the pa-
tient’s ability to sleep and function normally. If sleep is sig-
nicantly affected, and the patient becomes morbid, then
the symptoms are moderate to severe [5].
Symptoms of AR are triggered by inammatory me-
diators such as histamine and leukotrienes released as a
result of increased immunoglobulin E (IgE) production from
plasma cells. This increased production of IgE is mediated
by cytokines released from inammatory T cells invading
the mucosa of the nasal cavity in response to the expo-
sure of the mucosa to exogenous allergens [6]. Vit. D is
a fat-soluble vitamin that is well known for its role in calci-
um homeostasis and bone integrity. More recently, studies
have shown the role of vit.D in many allergic and immune
conditions, where receptors for the active form of vit. D (1,
25-dihydroxyvitamin D3) have been discovered on the sur-
face of almost all types of inammatory cells and this has
linked vit.D to immunity and immune diseases [7, 8].
Regarding the specic role of vit. D in AR, a literature
search has shown a discrepancy in ndings. For exam-
ple, Wjst and Hyppönen found that the incidence of AR in-
creases with serum levels of vit. D in Finland [9]. Similarly,
it was found that the incidence of AR was higher in adults
who have received vit. D supplementation during infancy
[10]. Conversely, Erkkola et al. observed that maternal vit.
D intake reduces the risk of AR in children at the age of 5
years [11]. Another study conducted in Iran showed that
the prevalence of severe vit. D deciency was much higher
in patients with AR [12]. Likewise, it was found by Sudiro
et al. that vit. D deciency can be related to AR and its
severity in Indonesia [3].
Accordingly, this study aims at examining the correla-
tion between vit. D levels and AR in a sample population
of the city of Mosul, Nineveh province in the north of Iraq.
Material and Methods
Study design and methodology
This study was conducted in Mosul city from March to Oc-
tober 2018 and involved two groups; the rst group com-
prised AR patients diagnosed in a private fully equipped
otolaryngology clinic by the rst author as having allergic
rhinitis (AR group). Forty-nine patients were clinically di-
agnosed, and nasal endoscopy was performed on every
patient to exclude other conditions such as sinusitis, na-
sal polyposis, and nasal septal deviation. The diagnosis
was made according to the “AR and its Impact on Asthma”
(ARIA) guidelines, a runny nose and nasal obstruction as
the main complaints [5]. The second group included 50
apparently healthy volunteers with no history of AR, aged
between 20 and 50 years, and regarded as the control
group. IgE was measured in both groups. Both groups
enrolled had blood tests in order to determine their 25-hy-
droxyvitamin D3 serum levels. The study was approved by
the Health Research Ethics Committee at the College of
Medicine, University of Mosul (No: UOM/COM/2019/2). A
written consent form was provided for each subject par-
ticipating in the study with full awareness of the details.
Blood samples were collected from all the subjects, and
25-hydroxyvitamin D3 serum level was measured by the
immunoassay method using the Dimension® Suite from
Siemens. A vit. D level of less than 10 ng/ml was consid-
ered severe vit. D deciency, whereas a vit. D level of 10-
12 ng/ml was considered moderate vit.D deciency, while
a vit. D level of 12.1-20 ng/ml was regarded as vit. D insuf-
ciency; nally, a serum level of more than 20 ng/ml was
considered normal [13]. None of the participants in both
groups was receiving vit. D supplements. The Serum IgE
level was measured by the immunoassay method (Allegro,
Algeria). AR is classied as intermittent if symptoms are
present in less than four days a week or less than four
weeks a time. Perennial AR means symptoms persist for
four days or more a week and four weeks or more a time.
AR is classied as moderate to severe if one or more of the
following is present: abnormal sleep, impairment of daily
activity, abnormal work at school, or troublesome symp-
toms. If none of the above symptoms is present, it is re-
garded as mild AR [5].
Inclusion criteria included patients with AR attending
the private clinic of the rst author with age ranging be-
tween 18-55 years.
Exclusion criteria involved AR patients who have a
body mass index (BMI) greater than 26 kg/m2, patients
with inammatory or immunological conditions such as
asthma, nasal polyposis, and rheumatoid arthritis, patients
with chronic illnesses such as diabetes mellitus, renal in-
sufciency, and abnormal vit. D metabolism, in addition to
patients receiving chronic or recent therapy with steroids,
antihistamines, vit. D supplements and chemotherapeutic
agents.
Data analysis
All values were expressed as the mean ± standard devia-
tion (SD) or standard error of mean (SEM) where indicat-
ed. Student’s paired t-test for single data comparison was
performed. Pearson’s correlation was used to analyze the
relationship between the studied parameters. GraphPad
Prism 8.0 software was utilized to assess the statistical
signicance (P < 0.05) of any difference between the mean
values.
Results
The studied sample was divided into two groups: the AR
group included AR patients of the same age, sex and
weight as the control group, which included healthy volun-
teers. Characteristics of the studied population are sum-
marized in Table 1, which represents the age, sex, weight,
and BMI status of the studied population.
Journal of Medicine and Life Vol. 13, Issue 4, October-December 2020, pp. 463–468
465
Most patients in the AR group (71%) had moderate to se-
vere persistent AR. At the same time, the mild intermittent
class was shown to be the least presented when compared
to the other investigated classes of the disease, as shown
in Table 2.
The mean level of IgE and vit. D was found to be 30.8
and 23.3 ng/ml, respectively, in the control group and
326.3 and 10.2 ng/ml, respectively, in the AR group. Nine-
ty-three percent of AR patients have shown a deciency
in vit. D levels, where 56% of this group showed severe
deciency. On the other hand, 34% of the control group
has shown an insufcient level of vit. D. Sixty-four percent
of AR patients have shown serum level of IgE at values
ranging between 100-299 ng/ml, while 25% and 11% of
AR patients have shown higher serum levels of IgE at val-
ues ranging between 300-599 ng/ml and 600-1000 ng/ml,
respectively. The prevalence of low levels of vit. D in the
AR group was signicantly higher compared to the control
group (P < 0.001), as shown in Figure 1. The serum level
of IgE in the AR group was signicantly higher than that
in the control group (P < 0.001), as illustrated in Figure
2. The correlation of serum levels of IgE with vit. D in the
control group was found to be statistically insignicant (P
> 0.05). The correlation coefcient (r) between the varia-
bles was 0.1197, which does not reect a signicant cor-
relation between the two variables (Figure 3). However, a
statistically signicant negative correlation was observed
between the serum IgE and vit. D levels in the AR group
(P < 0.05). The correlation coefcient (r) between the var-
iables is -0.3643, which reects the negative correlation
between the two variables (Figure 4). To further link the
severity of AR to vit. D deciency, serum IgE level in the
moderate-severe class (which represents the majority of
AR patients in this study) was correlated to the vit. D level
and the results have shown a stronger negative correlation
between the studied variables at r=-0.6680 and a P-value
of less than 0.01 (Figure 5).
Discussion
Vitamin D is an essential nutrient required for healthy
bones and the immune system. It has two major forms:
(D2; ergocalciferol and D3; cholecalciferol); both forms can
be obtained from foods. However, only vitamin D3 can be
made by the human body [14]. The parameter that is di-
rectly tested to measure vitamin D3 level in the blood is
25(OH)D3. However, 1,25(OH)2D3 is the most biologically
active metabolite of vitamin D3 [15].
The association between immune diseases and
1,25(OH)2D3 had been documented since 1984. A link
between allergic disorders (especially asthma) and vit. D
levels had been reported in many epidemiological studies
[16]. Several mechanisms were reported to be involved in
the immune modulation effect of 1,25(OH)2D3 on immune
cells and some cytokines. Among these mechanisms,
T-cell proliferation inhibition, suppressing the differentiation
and transcription of Th17 cells, enhancing Th2 cell devel-
opment, decreasing macrophage inammation, T-cell stim-
ulation and inhibiting immunoglobulin secretion, including
IgE secretion can be noted [17]. The immunoregulatory
effect of vitamin D3 provides a good base for a correlation
between AR and vitamin D3 serum level; AR pathogenesis
comprises phenotype transfer of Th1 to Th2 in the produc-
tion of CD4+ T cells in addition to the involvement of Th17
and T-reg cells in the disease course. Induction of Th1 shift
to Th2 by augmenting Th2 development and inhibition of T
cell proliferation are the main immunomodulatory actions
of vitamin D3 on top of subdues processes of differentia-
tion and transcription of Th17 cells and aids the stimulation
of Foxp3+ T-reg cells [18].
Age, weight, type of food, skin pigment, lifestyle, resi-
dence and sun exposure are factors that could affect vit. D
levels in one way or another. Elderly, as well as overweight
or obese individuals, usually have low vit. D levels. Also,
Studied sample Age (years) Number (M/F) Weight (kg) BMI (kg/m2)
Control group 30.57 ± 6.5 50 (22/28) 71.1 ± 7.69 24.7 ± 1.44
AR group 28.1 ± 9.9 49 (20/29) 70.7 ± 18 25.8 ± 6
Table 1: Characteristics of the studied groups.
Results are expressed as mean ± S.D.; M: male, F: female.
Table 2: Classication of AR group according to severity.
Class % (N) of patients affected
Mild intermittent 2.04 (1)
Mild persistent 6.12 (3)
Moderate-severe intermittent 20.4 (10)
Moderate-severe persistent 71.42 (35)
(N)= Number of patients.
Journal of Medicine and Life Vol. 13, Issue 4, October-December 2020, pp. 463–468
466
diets low in sh and dairy are associated with vit. D de-
ciency. People with dark skin, persons frequently using
sunscreen, wearing long sleeve shirts, head cover, trave-
ling by car, having a sedentary lifestyle, limited availability
of the sun in the living area, as well as variation in sun
exposure due to season variation, time of the day expo-
sure and atmospheric components, could all affect the vit.
D status [19, 20]. Iraq is a subtropical country, where sum-
Figure 1: Serum vitamin D level in the studied groups.
Data are expressed as mean ± SEM. ***P < 0.001 represents
a difference of statistical signicance between AR and control
group. Student’s paired t-test was used for statistical com-
parison.
Figure 2: Serum IgE level in the studied groups.
Data are expressed as mean ± SEM. ***P < 0.001 represents
a difference of statistical signicance between AR and control
group. Student’s paired t-test was used for statistical com-
parison.
Figure 3: Serum IgE level versus serum vitamin D level in the
control group.
(r): Pearson correlation coefcient between the two investigated
variables. Statistically non-signicant correlation is shown at P
> 0.05. IgE-C and Vit.D-C: Serum level of IgE and vit. D in the
control group.
Figure 4: Serum IgE level versus serum vitamin D level in AR
group.
(r): Pearson correlation coefcient between the two investigated
variables. Statistically signicant negative correlation is shown
at *P < 0.05. IgE-AR and Vit.D-AR: Serum level of IgE and vit. D
in the AR group.
Journal of Medicine and Life Vol. 13, Issue 4, October-December 2020, pp. 463–468
467
mer is sunny, and winter is mostly cloudy. Vit. D deciency
is expected to be prevalent during winter, so we performed
our study during spring, summer and autumn in order to
avoid this effect.
This study was directed to explore the relationship
between vit. D serum level and the prevalence of AR in
both patients and healthy subjects. Total serum IgE is
not helpful for the diagnosis of AR according to the ARIA
guidelines. Despite this, IgE was investigated in this study.
Our hypothesis to include IgE was that vit. D is an immu-
nomodulator, and its deciency can lead to an increased
allergic response. Therefore, IgE may be associated with
vit. D deciency for the same reason.
The study revealed that 93% of patients diagnosed
with AR had a deciency in vit. D levels. We also found
an association between IgE levels and vit. D deciency in
these patients; this association was found to be stronger in
patients with moderate to severe persistent AR.
The present study showed a signicant difference in
the mean serum level of vit. D between the healthy group
and the AR group (p < 0.001). The statistics revealed that
most of the patients were diagnosed as having the severe
class of the disease (91.8%); the low number of patients
in our study with mild AR (intermittent - 1 patient, mild to
severe - 3 patients) may be explained by the fact that these
patients commonly depend on self-prescribed medications
due to mild symptoms.
Our study showed that the prevalence of vit. D de-
ciency is obvious among the AR group, which matches
the ndings of Sudiro et al., who reported a correlation
between the severity of vit. D deciency and the severity
of AR. In addition, Vatankhah V. et al. described the AR
group as a vit. D decient group in comparison to people
with normal vit. D levels [3, 21]. However, another study
reported no correlation between vit. D levels and the se-
verity of AR [22].
Hypovitaminosis D was reported in many literature
studies conducted in the Middle East, revealing that, de-
spite the plentiful sunny climate in this part of the world,
the region registers low vit. D levels among different age
groups. Factors like insufcient vit. D intake during infan-
cy, economic causes, inadequate sun exposure, traditional
clothing style, and urban living may contribute to the low
level of vit. D. The ndings of our study are consistent with
these global annotations [23].
The serum concentrations of vit. D that are associated
with deciency, adequacy, and optimum overall health are
still tremendously questionable. The Institute of Medicine
(IOM) states that the serum concentrations of vit. D less
than 12 ng/ml may predispose people to a risk of vit. D
deciency. Serum levels between 12–20 ng/ml predispose
to a potential risk of inadequacy. Almost everyone is con-
sidered to have appropriate vit. D levels at serum values
greater than 20 ng/ml. Additionally, the committee of IOM
reported that 20 ng/ml is the amount of serum vit. D serving
the needs of about 97.5% of the population. Additionally,
serum levels greater than 50 ng/ml may associate with
possible adverse effects [13].
Our study suggests that vit. D level is one of the pa-
rameters that have to be checked in AR patients, in ac-
cordance with the ndings of other similar studies which
correlate vit. D deciency to AR [3, 24]. The results of the
present study also support the recommendations to adjust
vit. D status among different age groups [23]. Detailed in-
formation about the lifestyle of the participants and anal-
ysis of the data concerning factors affecting vit. D serum
levels, either directly or indirectly, are considered a limita-
tion of this study.
Figure 5: Serum IgE level versus serum vitamin D level in patients with moderate-severe persistent AR.
(r): Pearson correlation coefcient between the two investigated variables. Statistically signicant negative correlation is shown at **P
< 0.01. IgE-AR and Vit.D-AR: Serum level of IgE and vit. D in the AR group.
Journal of Medicine and Life Vol. 13, Issue 4, October-December 2020, pp. 463–468
468
Conclusion
Vit. D deciency is linked with the severity of AR, and mon-
itoring serum vit. D levels is advisable in this group of pa-
tients. In addition, adjustment of vit. D levels is sensible in
apparently healthy people as the results of this study have
found a subclinical level of vit. D in a signicant number
of healthy volunteers. Moreover, future studies are recom-
mended to investigate the role of the administration of vit.
D as an add-on therapy for AR patients that have a low
level of vit. D.
Conict of Interest
The authors declare that there is no conict of interest.
References
1. Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis.
The Lancet. 2011. p. 2112–22.
2. Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica
GW, Casale TB, et al. Allergic Rhinitis and its Impact on Asth-
ma (ARIA) guidelines: 2010 Revision. J Allergy Clin Immunol.
2010;126(3):466–76. doi:10.1016/j.jaci.2010.06.047.
3. Sudiro M et al. Vitamin D deciency is correlated with severity of
allergic rhinitis. Open Access Libr J. 2017;4(08):1–9.
4. Alsamarai AM, Alwan AM, Ahmad AH, Salih MA, Salih JA, Alda-
bagh MA, et al. The relationship between asthma and allergic rhi-
nitis in the Iraqi population. Allergol Int. 2009;58(4):549–55.
5. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its
Impact on Asthma (ARIA) 2008 update (in collaboration with the
World Health Organization, GA(2)LEN and AllerGen). Allergy.
2008;63 Suppl 86:8–160. doi:10.1111/j.1398-9995.2007.01620.x.
6. Small, P. and Kim H. Allergic rhinitis. Allergy, Asthma Clin Immunol.
2011;7(1):S3.
7. Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-di-
hydroxyvitamin D3, and the immune system. The American journal
of clinical nutrition. 2004. p. 1717S-1720S.
8. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D:
Modulator of the immune system. Current Opinion in Pharmacol-
ogy. 2010. p. 482–96.
9. Wjst, M. and Hyppönen E. Vitamin D serum levels and allergic
rhinitis. Allergy. 2007;62(9):1085–1086.
10. Hyppönen E, Sovio U, Wjst M, Patel S, Pekkanen J, Hartikainen
AL, et al. Infant vitamin D supplementation and allergic conditions
in adulthood: Northern Finland birth cohort 1966. Annals of the
New York Academy of Sciences. 2004;1037: 84–95. doi:10.1196/
annals.1337.013.
11. Erkkola M, Kaila M, Nwaru BI, Kronberg-Kippilä C, Ahonen S, Ne-
valainen J, et al. Maternal vitamin D intake during pregnancy is
inversely associated with asthma and allergic rhinitis in 5-year-old
children. Clin Exp Allergy. 2009;39(6):875–82.
12. Arshi S, Ghalehbaghi B, Kamrava S-K, Aminlou M. Vitamin D se-
rum levels in allergic rhinitis: any difference from normal popula-
tion? Asia Pac Allergy. 2012;2(1):45–8.
13. Ross AC, Taylor CL, Yaktine AL, Del Valle HB (2011) Dietary ref-
erence intakes for calcium and vitamin D. National Academies
Press,Washington (DC).
14. Kamen, D. L. and Tangpricha V. Vitamin D and molecular actions
on the immune system: Modulation of innate and autoimmunity. J
Mol Med. 2010;88(5):441–50.
15. Tian, H.-Q. and Cheng L. The role of vitamin D in allergic rhinitis.
Asia Pac Allergy. 2017;7(2):65–73.
16. Provvedini, D. M., Deftos, L. J. and Manolagas SC. 1,25-Dihy-
droxyvitamin D3 receptors in a subset of mitotically active lym-
phocytes from rat thymus’,. Biochem Biophys Res Commun.
1984;121(1):277–83.
17. Wang, Y., Zhu, J. and DeLuca HF. Where is the vitamin D recep-
tor? Arch Biochem Biophys. 2012;523(1):123–33.
18. 18. Di Rosa M et al. Immuno-modulatory effects of vita-
min D3 in human monocyte and macrophages. Cell Immunol.
2012;280(1):36–43.
19. Puri S et al. Vitamin D status of apparently healthy schoolgirls from
two different socioeconomic strata in Delhi: Relation to nutrition
and lifestyle. Br J Nutr. 2008;99(4):876–82.
20. Mazahery, H. and von Hurst PR. Factors affecting 25-hydroxyvi-
tamin D concentration in response to vitamin D supplementation.
Nutrients. 2015;7(7):5111–42.
21. Vatankhah V et al. Comparison vitamin D serum levels in allergic
rhinitis patients with normal population. Rev Française d’Allergolo-
gie. 2016;56(7–8):539–43.
22. Dogru M, Suleyman A. Serum 25-hydroxyvitamin D3 levels in chil-
dren with allergic or nonallergic rhinitis. Int J Pediatr Otorhinolaryn-
gol. 2016;80:39–42.
23. El-Rassi R, Baliki G, FulheihanG (2009) Vitamin D status in Mid-
dle East and Africa. IOP Publishing International Osteoporosis
Foundation. https://www.aub.edu.lb/fm/CaMOP/publications/Vita-
minD-status-in-the-Middle-East-and-North-Africa.pdf. Accessed
26 December 2019.
24. Oren, E., Banerji, A. and Camargo CA. Vitamin D and atopic dis-
orders in an obese population screened for vitamin D deciency. J
Allergy Clin Immunol. 2008;121(2):533–4.
