Al-Azhar Med. J.
DOI: 10.12816/0038267
Vol. 46(2), April, 2017, 443-454
INTERLEUKIN (IL)-17 AS A BIOMARKER IN
ASSESSMENT OF BRONCHIAL ASTHMA
SEVERITY
By
Eglal M. Kenawy , Hafez Abd El-Hafeez,
Nagwa Abd El-Ghaffar Mohamed* and Mahmoud M.A. Naeem
Internal Medicine Department, Faculty of Medicine - Al-Azhar University and
*Clinical and Chemical Pathology Department, National Research Center– Cairo
ABSTRACT
Background: Asthma is a serious global health problem affecting all age groups. Cytokines from T-helper 2
cells are believed to be critical contributors of asthma.
Objective: Measuring the serum levels of IL-17 as non-invasive biomarkers to assess asthma severity.
Patients and Method: A prospective case controlled study included forty patients were recruited from the
outpatient clinic and inpatient of Internal Medicine Department, Al-Hussein University Hospital, Al-Azhar
University divided into two equal groups (mild asthma and severe asthma) compared with twenty healthy
non-smoker subjects. Total serum level of IL 17 and serum IgE was measured by ELISA technique.
Complete blood count (CBC), pulmonary function tests (spirometry) and skin peak test were done for all
patients.
Results: A significant increase in body mass index (BMI) and age were found in patients with severe asthma
compared with those with mild asthma and normal control. Also, patients with severe asthma have more
airflow limitation, with a higher serum level of IL-17, IgE, and the number of eosinophils than patients with
mild asthma. Significant increase was found in the serum level of IL-17, IgE, the total count of WBCS the
number of eosinophils and the number of platelets in asthmatic patients compared with normal control. IL17
has positively correlated with the serum level of IgE, the number of eosinophils, BMI, the age of patients,
and negatively correlated with pulmonary function tests. By ROC analysis, a cutoff point for IL – 17 >51.5
Pg/ml, IgE >60IU/ml and the number of eosinophils >2.8% in the mild form of asthma, while the cutoff
values for IL17>92.9Pg/ml, IgE>162.0IU/ml and the number of eosinophils >4.1%) in the severer form of
asthma. Sensitivity, specificity and positive predictive value for IgE level in mild asthma were 85%, 80% and
77.8% respectively, while in severe asthma 65%, 85% and 83% respectively. Moreover, sensitivity,
specificity, positive predictive values for IL17 in mild asthma were 97.5%, 100% and 100% respectively,
while in severe asthma were 100%, 100% and 100% respectively.
Conclusion: Simple spirometric parameters (bedside test) were a good predictive tool for assessment asthma
severity. Among laboratory tests, IL17 was the best biomarker for diagnosis and prediction of asthma
severity in asthmatic patients than IgE.
Keywords: Asthma, IL17, IgE, eosinophils, obesity.
rising up to 10% of the population in
developed
countries (Nanzer and
Menzies-Gow, 2014). Asthma is charac-
INTRODUCTION
Asthma is associated with increase
morbidity and mortality with a prevalence
443
444
EGLAL M. KENAWY et al
terized by bronchoconstriction, airway
hyperreactivity, inflammation, mucus
hypersecretion, and remodeling of the
airway. These processes are coordinated
by a complex cytokine network (Ota et
al., 2014).
IL-17 is a one of this cytokine which
enhances T-helper 2 (Th2) cell-mediated
eosinophilic airway inflammation in
asthma. Many studies were done to obtain
the role of IL17 in asthma, one of them
had demonstrated that inhibition of IL-17
can reduce antigen-induced airway
inflammation,
bronchial
hyperresponsiveness and Th2 cytokine levels in
animal models of asthma (Park and Lee,
2010).
PATIENTS AND METHODS
Patients: Forty adult patients with asthma
were recruited from the outpatient clinic
and in-patient of Internal Medicine
Department,
Al-Hussein
University
Hospital, Al-Azhar University from
1/2015 to 6/2015. All patients were above
the age of 18 years, nonsmoker asthmatic
patients with variable severity with no
other co-morbidities.
Patients have one or more of the
following were excluded; concomitant
infection, chronic obstructive pulmonary
disease (COPD), gastro-esophageal reflux
disease (GERD), liver disease, chronic
rhinitis, malignancy, cystic ? brosis,
interstitial lung disease, auto-immune
disease and untreated cardiac failure.
Asthmatic patients were classified
according to GINA guidelines into mild
persistent and severe persistent according
to FEV1, frequency of symptoms,
nocturnal symptoms and affection of
exacerbations to sleep and activity.
Patients were divided into two equal
groups (20 patients in each group): group
1: (10 males and 10 females) with severe
bronchial asthma; group 2: (10 males and
10 females) with mild bronchial asthma
compared with 20 apparently healthy
control 10 males and 10 females forming
group 3.
Methods: All participants were exposed
to the following after their consents: Full
clinical examination, chest radiograph
(chest X-ray and CT if needed to exclude
other pathology), spirometry and allergy
skin prick test (SPT).
Baseline spirometric study; including
forced vital capacity (FVC), Forced
expiratory volume in first second (FEV1),
(FEV1/FVC) ratio and peak expiratory
flow (PEF) (MiniSpir, MIR S.r.l. via Del
Maggiolino 125, 00155 Roma – Italy).
All pulmonary function data were
expressed as percent of predicted value.
The FEV1/FVC ratio is normally greater
than 0.75 to 0.80 and a reduced ratio of
FEV1 to FVC indicates airflow limitation
Assessing the SPT; Positive and
negative controls were measured first. The
negative control excluded. The largest
diameter of the wheal of each particular
test is measured, a positive being a wheal
INTERLEUKIN (IL)-17 AS A BIOMARKER IN ASSESSMENT OF BRONCHIAL ...
of ≥ 3 mm in diameter (Heinzerling et al.,
2014).
Laboratory Work:
Laboratory investigations included:
Complete Blood Count (CBC) esp.
eosinophilic count, total serum IgE and
serum Interleukin (IL)-17.
Five mls of venous blood samples were
taken from each subject participating in
the study and divided into aliquots: The
1st aliquot about 1.5 mls of venous blood
was added to tube containing EDTA for
determination of complete blood picture
on coulter counter T890 (coulter counter,
Harpenden, UK). The 2nd aliquot was 3.5
ml was left to clot and then the serum was
separated by centrifugation at 1000g for
15 min and stored at -20°C for
determination, total IgE and IL-17.
The Serum IgE was measured by
quantitative sandwich ELISA and the kit
was supplied by Abcam (330 Cambridge
Science
Park,
Cambridge,
UK)
(Mehmedović et al., 2012).
The human IL-17A ELISA is an
enzyme-linked immunosorbent assay for
the quantitative detection of human IL17A. The kit was supplied from IBL
International GmbH (Flughafenstr. 52A,
22335 Hamburg, Germany) (Karabulut
et al., 2016).
445
Statistical analysis: Data were statistically analyzed using statistical package for
social sciences (SPSS) version 23.0 for
windows. Data are presented as the Mean ±
standard deviation (SD), frequency, and
percentage. Categorical variables were
compared using the chi-square (χ2).
Continuous normally distributed variables
were compared using One Way Analysis of
Variance (ANOVA) followed by post hoc
analysis using LSD test. Pearson
correlations coefficients were used to assess
the bivariate correlations between variables.
A receiver operating characteristic (ROC)
curve analysis was performed. The area
under the curve (AUC) was also used to
determine the ability of IgE, IL17 levels to
diagnose asthma severity. The level of
significance was accepted if the P value <
0.05.
RESULTS
Sixty subjects, 30 were males and 30
females, were classified into three groups
20 patients with severe asthma, 20
patients with mild asthma, and 20 normal
subjects were taken as control, with mean
age of the studied sample was 27.03±7.48
years and body mass index (BMI)
25.22±3.09 (Table 1).
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EGLAL M. KENAWY et al
Table (1): Demographic characteristics of the studied groups.
Variable
No. (N= 60)
%
Group
Severe asthma
Mild asthma
Control (non asthmatic)
20
33.4
20
33.3
20
33.3
Gender
Male
Female
30
50.0
30
50.0
Age (Years) (M ± SD)
27.03 ± 7.48
BMI (kg/m2 ) (M ± SD)
25.22 ± 3.09
Occupation
Student
Housewife
Manual worker
Marketer
Carpenter
Concierge
Dealer
Teacher
Farmer
Mechanic
Seller
Technician
Driver
House officer
Physician
Nurse
A significant increase in age and body
mass index (BMI) were found in patients
with severe asthma compared with those
with mild asthma p < 0.001 and p <
0.0013 respectively and normal control p
< 0.001 and p < 0.001 respectively. A
non-significant statistical difference in the
7
14
5
3
1
1
1
1
2
1
2
1
1
5
5
10
11.7
23.3
8.3
5.0
1.7
1.7
1.7
1.7
3.3
1.7
3.3
1.7
1.7
8.3
8.3
16.7
age and BMI between patients with mild
asthma and normal control group were
found, p=0.490 and p =0.090 respectively.
Significant elevation in serum level of IL
17, IgE, total white blood count (WBC),
eosinophils and platelet were found
between patients and normal control with
INTERLEUKIN (IL)-17 AS A BIOMARKER IN ASSESSMENT OF BRONCHIAL ...
P values < 0.001, 0.001 0.027, 0.001 and
0.020 respectively. Also, the significant
increase in serum level of IL17, IgE and
eosinophils in patient with severe asthma
than those with mild asthma were found
with P values < 0.001, 0.001 and 0.001
respectively.
Comparing
spirometric
parameters of patients with normal
control, we found a limitation of airflow
447
in patients than the normal control with p value for FVC%, FEV%, FEV1/FVC and
PEF were 0.001, 0.001, 0.001 and 0.001
respectively, with more airflow limitation
in severe asthmatic patients than those
with mild asthma p value of FVC%,
FEV%, FEV1/FVC and PEF were 0.001,
0.001, 0.001 and 0.001, respectively
(Table 2).
Table (2): Some demographic and laboratory data for the three studied groups.
Mild asthma Severe asthma Normal control
(N=20)
(N=20)
(N=20)
Variable
One Way
ANOVA
Post hoc analysis
by LSD test
Mean ±SD
Mean ±SD
Mean 0±SD
F
P-value
P1
P2
P3
Age (Years)
24.25 ± 2.50
32.05 ± 8.82
24.80 ± 2.50
12.593
0.001
0.490
0.001
0.001
BMI (kg/m2)
24.80 ± 2.52
27.29 ± 3.44
23.56 ± 1.95
9.847
0. 001
0.090 <0.001 0.013
IL – 17 (Pg/ml)
68.29 ± 13.63 130.97 ± 20.96
34.10 ± 6.91
215.228 0. 001 <0.001 <0.001 <0.001
T. IgE (IU/ml)
111.33 ± 92.50 400.95 ± 327.97
52.65 ± 62.09
17.390
0. 001
0.024 <0.001 0.001
HB (g/dl)
13.41 ± 1.01
13.93 ± 1.06
13.63 ± 1.12
1.203
0.308
0.518
0.399
0.121
WBCs (X103/mm3)
7.75 ± 1.33
7.75 ± 1.75
6.50 ± 1.81
3.884
0.027
0.017
0.032
1.000
Eosinophil %
4.60 ± 1.64
7.31 ± 2.75
2.22 ± 1.04
34.337
0. 001 <0.001 <0.001 0.001
237.00 ± 50.60
4.186
0.020
0.007
66.092
0. 001
0.028 <0.001 <0.001
Platelets (X103/mm3) 283.15 ± 51.78 275.20 ± 59.02
0.034
0.653
FVC %
95.20 ± 6.22
68.55 ± 13.15
99.95 ± 6.96
FVE1 %
68.95 ± 3.68
33.60 ± 7.36
99.15 ± 12.11 301.285 0. 001 <0.001 <0.001 <0.001
FEV1/FVC
70.85 ± 2.87
49.20 ± 6.94
98.40 ± 9.23
PEF %
64.60 ± 2.70
33.10 ± 9.61
97.80 ± 14.75 197.998 0. 001 <0.001 <0.001 <0.001
257.665 0. 001 <0.001 <0.001 <0.001
P1: Mild vs control; P2: Severe vs control; P3: Mild vs severe.
BMI: body mass index; IL - 17: Interleukin – 17; T. IgE: Total IgE; HB: Hemoglobin%; WBCs: White Blood Cells.
FVC: Forced Vital Capacity; FVE1: Forced Expiratory Volume in 1 Second; FEV1/FVC: the ratio of FEV1 to FVC;
PEF: Peak Expiratory Flow
Serum level of IL17 was positively
correlated with severity of asthma, serum
level of IgE, number of eosinophils, BMI,
age were p<0.001, 0.001, 0.001, 0.004 and
0.001 respectively, and
negatively
correlated to spirometric parameters
FVC%, FVE1%, FEV1/FVC%, PEF%
with P<0.001 for all (Table 3).
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EGLAL M. KENAWY et al
Table (3): Correlation the IL–17 level with some laboratory, spirometric, demographic
data.
IL – 17 (Pg/ml)
IL-17 (pg/ml)
Variables
r
0.589
0.138
0.070
0.785
– 0.017
– 0.510
– 0.560
– 0.524
– 0.663
0.317
0.610
T. IgE (IU/ml)
HB (g/dl)
WBCs (X103/mm3)
Eosinophil %
Platelets (X103/mm3)
FVC %
FVE1 %
FEV1/FVC %
PEF %
BMI (kg/m2)
Age (years)
A number of atopic patients in mild
asthmatic group was 11 (55.0%), while in
p
0.001
0.216
0.529
0.001
0.880
0.001
0.001
0.001
0.001
0.004
0.001
severe asthmatic, atopic patients 7 (35%)
with p< 0.522 (Table 4).
Table (4): Comparison of skin prick test in twenty patients with mild asthma compared
with twenty patients with severe asthma.
Severity of Asthma
Skin prick test
Skin prick test
Negative
Aspergellus. F
Tobacco
House dust
Mixed pollen
Mites
Cockroach, Mites
Candida
Aspergellus. F & Tobacco
Aspergellus. F & Mites
Tobacco & house dust
Mixed pollen & house dust
Severity of Asthma
Severe
Mild
(N = 20)
(N = 20)
7 (35.0%)
11 (55.0%)
3 (15.0%)
2 (10.0%)
4 (20.0%)
4 (20.0%)
0 (0.0%)
1 (5.0%)
1 (5.0%)
0 (0.0%)
0 (0.0%)
1 (5.0%)
1 (5.0%)
0 (0.0%)
1 (5.0%)
0 (0.0%)
1 (5.0%)
0 (0.0%)
1 (5.0%)
0 (0.0%)
1 (5.0%)
0 (0.0%)
0 (0.0%)
1 (5.0%)
p
0.522
INTERLEUKIN (IL)-17 AS A BIOMARKER IN ASSESSMENT OF BRONCHIAL ...
By ROC analysis of data we found a
cutoff point for IL – 17, IgE and number
of eosinophils in the mild form of asthma
(>51.5 Pg/ml, >60IU/ml and >2.8%
respectively), while the cutoff values for
IL17, IgE and number of eosinophils in
the severe form of asthma were
(>92.9Pg/ml, >162.0 IU/ml and >4.1%
respectively). The sensitivity, specificity
and positive predictive value for IgE level
in mild asthma were 85%, 80%, and
77.8% respectively, while in severe
asthma were 65%, 85% and 83%
respectively.
Moreover, the sensitivity, specificity
and positive predictive value for IL17 in
mild asthma were 97.5%, 100% and 100%
respectively, while in severe asthma were
(100%, 100% and 100%) respectively.
The sensitivity, specificity and positive
predictive value for IgE level in mild
asthma were 85%, 80%, and 77.8%
respectively, while in severe asthma 65%,
85% and 83% respectively. Moreover, the
sensitivity, specificity and positive
predictive value for IL17 in mild asthma
were
97.5%,
100%
and
100%
respectively, while in severe asthma were
100%, 100% and 100% respectively.
DISCUSSION
Cytokines from T-helper 2 cells are
believed to play a critical role in asthma.
In the last few years, IL-17, one of Thelper lymphocyte-associated cytokine
had been considered as another potentially
important mediator of asthma (Silverpil
and Lindén, 2012).
Many studies
with asthma to
different cluster,
clear picture for
were done on patients
categorize them into a
phenotypes to obtain a
the patients with severe
449
form of asthma. Moore and his coworker
(2010) made an algorithm approach to
obtain 5 clusters for the classi? cation of
disease severity. While Dursun and his
Colleagues (2014) stated that current
phenotyping proposals failed to cover all
severe asthma (SA). Thus, there is still
need further investigations in order to
explore validity and applicability of
phenotyping of SA. Furthermore Loureiro
and his Colleagues (2015) were
con? rmed many results of Moore et al by
using a biomarker and found other
parameters of interest such as age, weight,
blood eosinophilia. We found a significant
increase in serum level of IL-17 and IgE
in asthmatic patients than control group
while those with a higher serum level of
IL17, and IgE had a severe form of
asthma than other patients with asthma.
Various studies have reported the
expression of IL-17 and IgE was higher in
patients with bronchial asthma than that of
healthy control (Chen et al., 2010; Lu et
al., 2012; Robinson et al., 2013; Fn,
2016; Lv et al., 2016). However, an
increased immunoglobulin E (IgE)
production was reported by other’s
(Zeiger and Heller, 1995; Thomas et al.,
2003;Skiepko et al., 2009; Heidenfelder
et al., 2010) to be the strongest
predisposing factor for the development of
asthma and significantly correlated with
allergy as determined by the serum IgE
levels, while other researchers found a
negative association between IgE and
spirometric parameter (FEV1, FVC,
FEV1/FVC) in asthmatic patients than
healthy control (Anupama et al., 2005;
Satwaniet al., 2009; Mojtaba et al.,
2011). Moreover, Rotsides and his
coworkers (2010) were found a high
positive association between increased
450
EGLAL M. KENAWY et al
IgE and asthma severity in children and
concluded that serum IgE level is a strong
predictor for allergy in asthmatic children.
Other studies have reported that
increased serum IL-17 level as an
independent risk factor for severe asthma.
One possibility is that IL-17 could induce
the release of the inflammation factor IL-6
to cause neutrophil recruitment and
activation related to local inflammation of
the lungs (Sandeep et al., 2010; Agache
et al., 2010). Also, the increase of IL-17 in
SA compared with other forms of asthma
was found by Alyasin and his coworkers
(2013) suggest that it can be used to
predict asthma severity in children.
A numerous number of eosinophils can
be found in the bronchial airway in
eosinophilic asthma phenotype, and this
phenotype can be identified by peripheral
eosinophil count (Possa et al., 2013).
Interleukin-17 (IL-17) is an early trigger
of
the
T
lymphocyte-induced
inflammatory response and can induce
and activate the neutrophil recruitment to
the respiratory tract (Qu et al., 2013) and
also enhances T-helper 2 (Th2) cellmediated eosinophilic airway inflammation
in asthma (Park et al., 2010).Moreover, In
non-allergic
eosinophilic
asthma,
stimulation of epithelial air way by
microbes, pollutants and glycolipids
leading to release of epithelium-derived
cytokines IL-33, IL-25 and thymic stromal
lymphopoietin .This cytokines well
stimulate
and activate the innate
lymphoid cells (ILCs) via the (IL-17
receptor and this lead to produce high
amounts of IL-5 and IL-13 from the
(ILCs) leading to eosinophilia, mucus
hypersecretion and airway hyperreactivity.
(De Groot et al,2015).
We found increased level of IL17 was
positively correlated to number of
eosinophils, many previous researchers
linked between increased level of IL17
and increase number of neutrophils like
Sven and his colleagues (2015). While,
Hawas and his colleagues (2009) was
found levels of sputum IL 17 and serum
FAS were increased in bronchial asthma
patients especially in severe asthma with
decrease in eosinophils apoptotic ratio in
bronchial asthma patients than healthy
controls. Doe and his colleague (2010)
was found a potential role for the Th17
cytokines IL-17A and IL-17F in asthma
and COPD but did not demonstrate a
relationship with neutrophilic in? ammation.
Moreover, we observe a great variability
in the serum level of IgE among patients
in the same group (atopic patients had a
higher level than non-atopic). According
to the values obtained from rock analysis,
we suggest that serum IL17 is a good
biomarker for diagnosis and prediction of
asthma severity among atopic and nonatopic patients.
Also, we showed that the age and BMI
of patients with severe asthma were
significantly elevated than patients with
mild asthma and control group which can
be explained by aging increases morbidity
in patients with asthma. The pathogenesis
of adult-onset asthma are linked to several
metabolic and inflammatory components
which are common in other diseases like,
diabetes mellitus type 2 (DM2), cardiovascular diseases (CVD), obesity,
metabolic
syndrome
(MBO)
and
psychiatric diseases. In younger age
groups, allergy and obesity are the most
comorbidity associated with asthma
INTERLEUKIN (IL)-17 AS A BIOMARKER IN ASSESSMENT OF BRONCHIAL ...
451
(Kankaanranta et al., 2016). A metaanalysis has been performed to evaluate
the obesity as a risk factor for asthma and
reviled that the risk was 1.20 for
overweight and 1.43 for obese men. The
corresponding risk estimates for women
were 1.25 for overweight and 1.78 for
obesity (Guh et al., 2009). Anther US
epidemiological study was done and
reported odd ratio 1.29 for obese males
and 1.55 for obese females whom can
developed asthma in comparative with
normal weight populations (Wang et al.,
2015).
stage of asthma pathogenesis in the
development of bronchoconstriction,
airway
inflammation,
and
airway
remodeling. Platelets have the ability to
undergo chemotaxis, releasing various
important mediators, expressing adhesion
molecules on their surface and becoming
activated in response to mediators
released by other cells (Kornerup and
Page, 2007). Also, Benton and
Coworkers (2010) showed a significant
association
between
platelet
and
eosinophil activation in airways of human
subjects with asthma.
Mohanan and his Colleagues (2014);
Baffi and his Colleagues (2015)
explained why asthma develops more
frequently in obese than non-obese. This
may due to potential contributing factors
include changes in airway function due to
the effects of obesity on lung mechanics;
systemic inflammation through the release
of pro-inflammatory cytokines in obesity
(Sideleva and Dixon, 2014) and an
increased prevalence of co-morbidities,
genetic, developmental, hormonal via
adipocyte-derived hormones (adipokines),
which have immunomodulatory effects
(Sideleva et al., 2013) or neurogenic
influences or by increasing oxidative
stress (Sideleva et al., 2012). Kim and his
Colleagues (2014) were found in an
experimental obese mouse that obesity
causes airway inflammation and airway
hyper-reactivity associated with an
expansion of pulmonary IL-17+ ILC3
cells.
CONCLUSION
Also, our study showed a significant
increase in the platelet count in the
bronchial asthma groups compared with
normal subjects. Experimental evidence
suggested that platelets have a role in each
Simple spirometric parameters (bedside
test) are a good predictive tool for
assessment asthma severity. Among
laboratory tests, IL17 is the best
biomarker for diagnosis and prediction of
asthma severity in atopic and non–atopic
asthmatic patients than IgE.
REFERENCES
1. Agache I, Ciobanu C, Agache C and Anghel
M. (2010): Increased serum IL-17 is an
independent risk factor for severe asthma.
Respir Med., 104: 1131-1137.
2. Alyasin S, Karimi MH, Amin R, Babaei M
and Darougar S. (2013): Interleukin-17 Gene
Expression and Serum Levels in Children with
Severe Asthma. Iran J Immunol., 10(3):179-87.
3. Anupama N, Sharma MV, Nagaraja HS and
Bhat MR. (2015): The serum immunoglobulin
E Level reflects the severity of bronchial
asthma. Thai J Physiol Sci., 18: 35–40.
4. Baffi CW, Winnica DE and Holguin F.
(2015): Asthma and obesity: mechanisms and
clinical implications. Asthma Research and
Practice., 1(1):1.
5. Benton AS, Kumar N, Lerner J, Wiles AA,
Foerster M, Teach SJ and Freishtat RJ.
(2010): Airway Platelet Activation is Associa-
452
EGLAL M. KENAWY et al
ted with Airway Eosinophilic Inflammation in
Asthma. J Investig Med., 58(8): 987–990.
European standards. Clinical and Translational
Allergy, 3(1):1.
6. Chen J, Deng Y, Zhao J, Luo Z, Peng W,
Yang J, Ren L, Wang L, Fu Z, Yang X and
Liu E. (2010): The Polymorphism of IL-17 G152A was Associated with Childhood Asthma
and Bacterial Colonization of the Hypopharynx
in Bronchiolitis. Journal of Clinical Immunology., 30-4 539-545.
15. Kankaanranta H, Kauppi P, Tuomisto EL
and Ilmarinen P. (2016): Emerging
Comorbidities in Adult Asthma: Risks, Clinical
Associations, and Mechanisms. Hindawi
Publishing Corporation Mediators of In? ammation, Volume 2016, Article ID 3690628, 23
pages.
7.De Groot JC, Brinke AT and Bel EHD.
(2015): Management of the patient with
eosinophilic asthma: a new era begins. ERJ
Open Res.,1: 00024–2015.
16. Karabulut S, Afsar CU, Karabulut M, Al?s
H, K??
l c L, Cikot M, Yasasever CT and
Aykan NF. (2016): Evaluation of Serum
interleukin-17 (IL-17) levels as a diagnostic
marker in pancreatic adenocarcinoma. Journal
of Gastrointestinal Cancer., 47(1): 47–54.
8. Doe C, Bafadhel M, Siddiqui S, Desai D,
Mistry V, Rugman P, McCormick M, Woods
J, May R, Sleeman MA and Anderson IK.
(2010): Expression of the T Helper 17-Associated Cytokines IL-17A and IL-17F in Asthma
and COPD. Chest., 138(5):1140–1147.
9. Dursun AB, Erkekol FO and Kurt OK.
(2014): Severe Asthma Phenotyping: The
Applicability of Current Proposols in Daily
Practice. J. Lung Pulm Respir Res., 1(1): 3-9.
10. Fn N. (2016): Correlation of Serum IL-17 with
Level of Vitamin D and IgE in Asthmatic
Patients. British Journal of Pharmaceutical
Research., 11(1): 1-8.
11. Guh DP, Zhang W, Bansback N, Amarsi Z,
Birmingham CL and Anis AH. (2009): The
incidence of co-morbidities related to obesity
and overweight: asystematic review and metaanalysis. BMC Public Health, 9(1):1.
12. Hawas SA, EL-Kenawy MF and Abou ElEnin AK. (2009): Levels of Interleukin 17, Fas
and Eosinophil Apoptosis in Bronchial Asthma
Patients; Egyptian Journal of Medical
Microbiology., 18(3).
13. Heidenfelder B, Johnson M, Hudgens E,
Inmon J, Hamilton RG, Neas L and
Gallagher JE. (2010): Increased plasma
reactive oxidant levels and their relationship to
blood cells, total IgE, and allergen-specific IgE
levels in asthmatic children. J Asthma., 47(1):
106-11.
14. Heinzerling L, Mari A, Bergmann KC,
Bresciani M, Burbach G, Darsow U, Durham
S, Fokkens W, Gjomarkaj M, Haahtela T
and Bom AT. (2013): The skin prick test –
17. Kim HY, Lee HJ, Chang YJ, Pichavant M,
Shore SA, Fitzgerald KA, Iwakura Y, Israel
E, Bolger K, Faul J and DeKruyff RH.
(2014): IL-17 producing innate lymphoid cells
and the NLRP3 inflammasome facilitate
obesity-associated airway hyperreactivity. Nat
Med., 20(1): 54–61.
18. Kornerup KN and Page CP. (2007): The role
of platelets in the pathophysiology of asthma.
Journal Platelets., 18(5): 319-328.
19. Loureiro CC, Sa-Couto P, Todo-Bom A and
Bousquet J. (2015): Cluster analysis in
phenotyping a Portuguese. Rev Port Pneumol.,
21(6):299-306.
20. Lu H, Liu L, Cheng H, Zhang Y and Hua S.
(2012): Expression of interleukin 17 and IgE,
and its significance in patients with bronchial
asthma. African Journal of Pharmacy and
Pharmacology., 6(40): 2828-2831.
21. Lv H, Lu B, Qian XJ, Huang JA and Qiu T.
(2016): Serum IL-17 & eotaxin levels in
asthmatic patients with allergic rhinitis. Pak J
Med Sci., 32 (3):700-704.
22. Mehmedović A, Mesihović R, Prnjavorac B
and Kulo-Ćesić A. (2012): Evaluation of
serum IgG, IgM, IgA and IgE levels in patients
with chronic liver diseases. Medical Journal.,
18(2):81.
23. Mohanan S, Tapp H, McWilliams A and
Dulin M. (2014): Obesity and asthma:
Pathophysiology and implications for diagnosis
and management in primary care. Experimental
Biology and Medicine., 239: 1531–1540.
INTERLEUKIN (IL)-17 AS A BIOMARKER IN ASSESSMENT OF BRONCHIAL ...
24. Mojtaba E, MohammadAli SH, Davood K
and Hussein D. (2011): Increased Immunoglobulin E is associated with low respiratory
functional in asthma patients J. Bio. & Env.
Sci., 1 (6): 214-220.
25. Moore WC, Meyers DA, Wenzel SE, Teague
WG, Li H, Li X, D'Agostino Jr R, Castro M,
Curran-Everett D, Fitzpatrick AM and
Gaston B. (2010): Identification of Asthma
Phenotypes Using Cluster Analysis in the
Severe Asthma Research Program. Am J Respir
Crit Care Med., 181(4): 315-323.
26. Nanzer AM and Menzies-Gow A. (2014):
Defining severe asthma – an approach to find
new therapies. Eur Clin Respir J., 1: 10.
27. Ota K, Kawaguchi M, Matsukura S,
Kurokawa M, Kokubu F, Fujita J,
Morishima Y, Huang SK, Ishii Y, Satoh H
and Hizawa N. (2014): Potential Involvement
of IL-17F in Asthma. Journal of Immunology
Research., Volume 2014:602846.
28. Park SJ and Lee YC. (2010): Interleukin-17
regulation: an attractive therapeutic approach
for asthma. Respir Res., 11(1): 78.
29. Possa SS, Leick EA, Prado CM, Martins
MA and Tibério IF. (2013): Eosinophilic
inflammation in allergic asthma. Front.
Pharmacol., 4:46.
30. Qu N, Xu M, Mizoguchi I, Furusawa JI,
Kaneko K, Watanabe K, Mizuguchi J, Itoh
M, Kawakami Y and Yoshimoto T. (2013):
Pivotal Roles of T-Helper 17-Related
Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases. Clinical and Developmental
Immunology., 2013:968549.
31. Robinson KM, Manni ML, Biswas PS and
Alcorn JF. (2013): Clinical Consequences of
Targeting IL-17 and TH17 in Autoimmune and
Allergic Disorders. Curr Allergy Asthma Rep.,
13(6): 587-95.
32. Rotsides DZ, Goldstein IF, Canfield SM,
Perzanowski M, Mellins RB, Hoepner L,
Ashby-Thompson M and Jacobson JS.
(2010): Asthma, allergy, and IgE levels in NYC
head start children. Respir Med., 104(3):345-55.
33. Sandeep T, Roopakala MS, Silvia CR,
Chandrashekara S and Rao M. (2010):
453
Evaluation of serum immunoglobulin E levels
in bronchial asthma. Lung India., 27:138-40.
34. Satwani H, Rehman A, Ashraf S and Hassan
A. (2009): Is serum total IgE levels a good
predictor of allergies in children?. J Pak Med
Assoc., 59(10): 698-7029.
35. Sideleva O, Black K and Dixon AE (2013):
Effects of obesity and weight loss on airway
physiology and inflammation in asthma. Pulm
Pharmacol Ther., 26:455–8.
36. Sideleva O and Dixon A. (2014): The many
faces of asthma in obesity. J Cell Biochem.,
115:421–6.
37. Sideleva O, Suratt BT, Black KE, Tharp
WG, Pratley RE, Forgione P, Dienz O, Irvin
CG and Dixon AE. (2012): Obesity and
asthma: an inflammatory disease of adipose
tissue not the airway. Am J Respir Crit Care
Med., 186:598–605.
38. Silverpil E and Lindén A. (2012): IL-17 in
human asthma. Expert Rev Respir Med.,
6(2):173-86.
39. Skiepko R, Zietkowski Z, TomasiakŁozowska MM and Bodzenta-Łukaszyk A.
(2009): Anti-IgE therapy in persistent allergic
asthma. Przegl Lek., 66(3): 141-4.
40. Sven S, Scheers H, Marijsse G, Dilissen E,
Van Den Bergh A, Goeminne P, Van den
Brande P, Ceuppens J, Dupont L and
Bullens D. (2015): Th2-high asthma: a heterogeneous asthma population?: Clinical and
Translational Allergy., 5(2):1.
41. Thomas SS and Chhabra SK. (2003): A
study on the serum levels of interleukin-1beta in
bronchial asthma. J Indian Med Assoc., 101(5):
282- 286.
42. Wang L, Wang K, Gao X, Paul TK, Cai J
and Wang Y. (2015): Sex difference in the
association between obesity and asthma in U.S.
adults: findings from a national study.
Respiratory Medicine., 109(8): 955–962.
43. Zeiger RS and Heller S. (1995): The development and prediction of atopy in high-risk
children: follow-up at age seven years in a
prospective randomized study of combined
maternal and infant food allergen avoidance. J
Allergy Clin Immunol., 95:1179–1190.
EGLAL M. KENAWY et al
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إﻧﺗرﻟوﻛﯾن ١٧ -ﻛدﻟﯾل ﺣﯾوي ﻏﯾر ﻧﺎﻓذ ﻓﻲ ﺗﻘﯾﯾم ﺷدة
اﻟرﺑو اﻟﺷﻌﺑﻲ
إﺟﻼل ﻣﺤﻤﺪ ﻣﺤﻤﺪ ﻗﻨﺎوي -ﺣﺎﻓﻆ أﺣﻤﺪ ﻋﺒﺪ اﻟﺤﻔﯿﻆ -ﻧﺠﻮي ﻋﺒﺪاﻟﻐﻔﺎر ﻣﺤﻤﺪ* -ﻣﺤﻤﻮد ﻣﺤﻤﺪ ﻧﻌﯿﻢ
ﻗﺴﻢ اﻟﺒﺎطﻨﺔ اﻟﻌﺎﻣﺔ ﺑﻜﻠﯿﺔ اﻟﻄﺐ – ﺟﺎﻣﻌﺔ اﻷزھﺮ * ،ﻗﺴﻢ اﻟﺒﺎﺛﻮﻟﻮﺟﯿﺎ اﻹﻛﻠﯿﻨﯿﻜﯿﺔ واﻟﻜﯿﻤﯿﺎﺋﯿﺔ -اﻟﻤﺮﻛﺰ اﻟﻘﻮﻣﻰ ﻟﻠﺒﺤﻮث
ﻣﻘﺪﻣﺔ اﻟﺒﺤﺚ :اﻟﺮﺑﻮ ھﻮ ﻣﺸﻜﻠﺔ ﺻﺤﯿﺔ ﻋﺎﻟﻤﯿﺔ ﺧﻄﯿﺮة ﺗﺆﺛﺮ ﻋﻠﻰ ﺟﻤﯿﻊ اﻟﻔﺌﺎت اﻟﻌﻤﺮﯾﺔ .وﯾﻌﺘﻘﺪ أن
اﻟﺴﯿﺘﻮﻛﺎﯾﻦ اﻟﻨﺎﺗﺞ ﻣﻦ اﻟﺨﻼﯾﺎ اﻟﺘﺎﺋﯿﺔ ﻟﮭﺎ دور ﺣﺎﺳﻢ ﻓﻲ اﻟﺮﺑﻮ اﻟﺸﻌﺒﻲ .ﻓﻔﻲ اﻟﺴﻨﻮات اﻷﺧﯿﺮة ،ﯾﻌﺘﺒﺮ
إﻧﺘﺮﻟﻮﻛﯿﻦ) ١٧-وھﻮ اﺣﺪ ھﺬه اﻟﺴﯿﺘﻮﻛﺎﯾﻦ اﻟﻤﺮﺗﺒﻄﺔ ﺑﺎﻟﺨﻼﯾﺎ اﻟﺘﺎﺋﯿﺔ اﻟﻠﻤﻔﺎوﯾﺔ( وﺳﯿﻄﺎ ھﺎﻣﺎ ﻓﻲ اﻟﺮﺑﻮ
اﻟﺸﻌﺒﻲ.
اﻟﮭﺪف ﻣﻦ اﻟﺒﺤﺚ :ﯾﮭﺪف اﻟﺒﺤﺚ إﻟﻰ ﻗﯿﺎس ﻧﺴﺒﺔ اﻹﻧﺘﺮﻟﻮﻛﯿﻦ ١٧-ﻓﻲ اﻟﺪم ﻛﻤﺆﺷﺮ ﺣﯿﻮي ﻏﯿﺮ ﻧﺎﻓﺬ ﻟﺘﻘﯿﯿﻢ
ﺷﺪة اﻟﺮﺑﻮ اﻟﺸﻌﺒﻲ.
اﻟﻤﺮﺿﻰ وطﺮق اﻟﺒﺤﺚ :ﺗﻀﻤﻦ اﻟﺒﺤﺚ ﺛﻼث ﻣﺠﻤﻮﻋﺎت :ﻋﺸﺮون ﻣﺮﯾﻀﺎ ﺑﺤﺴﺎﺳﯿﺔ ﺻﺪر ﺷﺪﯾﺪة،
وﻋﺸﺮﯾﻦ ﻣﺮﯾﻀﺎ ﺑﺤﺴﺎﺳﯿﺔ ﺻﺪر ﻣﺘﻮﺳﻄﺔ ،وﻋﺸﺮﯾﻦ ﺷﺨﺼﺎ ً طﺒﯿﻌﯿﺎ ﻛﻤﺠﻮﻋﺔ ﺣﺎﻛﻤﺔ ،وﺗﻢ اﺧﺬ
اﻟﻤﺮﺿﻰ ﻣﻦ اﻟﻌﯿﺎدة اﻟﺨﺎرﺟﯿﺔ واﻟﻘﺴﻢ اﻟﺪاﺧﻠﻲ ﻟﻘﺴﻢ اﻷﻣﺮاض اﻟﺒﺎطﻨﺔ ﺑﻤﺴﺘﺸﻔﻰ اﻟﺤﺴﯿﻦ اﻟﺠﺎﻣﻌﻰ
ﺑﺠﺎﻣﻌﺔ اﻷزھﺮ ﻓﻰ اﻟﻔﺘﺮة ﻣﻦ ﯾﻨﺎﯾﺮ ٢٠١٥اﻟﻰ ﯾﻮﻧﯿﻮ .٢٠١٥
اﺷﺘﻤﻠﺖ ﺧﻄﺔ اﻟﺒﺤﺚ ﻋﻠﻰ ﺗﻘﯿﯿﻢ ﺟﻤﯿﻊ اﻟﻤﺮﺿﻰ ﻛﺎﻵﺗﻰ :أﺧﺬ اﻟﺘﺎرﯾﺦ اﻟﻤﺮﺿﻰ اﻟﻜﺎﻣﻞ ،اﻟﻔﺤﺺ
اﻹﻛﻠﯿﻨﯿﻜﻰ ،وﻋﻤﻞ وظﺎﺋﻒ اﻟﺘﻨﻔﺲ ،ﺻﻮرة دم ﻛﺎﻣﻠﺔ ،وﻗﯿﺎس ﻧﺴﺒﺔ اﻷﺟﺴﺎم اﻟﻤﻨﺎﻋﯿﺔ اﻟﻤﻀﺎدة ﺑﺎﻟﺪم،
وﻗﯿﺎس ﻣﻌﺪل اﻹﻧﺘﺮﻟﻮﻛﯿﻦ ١٧-ﻓﻲ اﻟﺪم.
ﻧﺘﺎﺋﺞ اﻟﺒﺤﺚ :أظﮭﺮت اﻟﻨﺘﺎﺋﺞ وﺟﻮد إرﺗﺒﺎط ﻛﺒﯿﺮ ﺑﯿﻦ ﻓﺮط إﺳﺘﺠﺎﺑﺔ ﻣﺠﺮى اﻟﮭﻮاء وﺑﯿﻦ ﻧﺴﺒﺔ اﻷﺟﺴﺎم
اﻟﻤﻨﺎﻋﯿﺔ اﻟﻤﻀﺎدة ﻣﻊ إرﺗﻔﺎع ﻣﻌﺪل اﻹﻧﺘﺮﻟﻮﻛﯿﻦ ١٧-ﻓﻲ ﻣﺮﺿﻲ اﻟﺮﺑﻮ اﻟﺸﻌﺒﻲ .ﻛﻤﺎ أظﮭﺮت اﻟﻨﺘﺎﺋﺞ أن
ﻗﯿﺎس ﻣﻌﺪل اﻹﻧﺘﺮﻟﻮﻛﯿﻦ ١٧-ﻓﻲ اﻟﺪم ﯾﻤﻜﻦ اﺳﺘﺨﺪاﻣﮫ ﻟﻠﺘﺸﺨﯿﺺ واﻟﺘﻨﺒﻮء ﺑﺸﺪة اﻟﺮﺑﻮ اﻟﺸﻌﺒﻲ .
اﻟﺨﻼﺻﺔ :ﻋﻤﻞ وظﺎﺋﻒ اﻟﺘﻨﻔﺲ ﻟﻠﻤﺮﺿﻰ ﻣﻦ اﻷﺷﯿﺎء اﻟﻤﮭﻤﺔ واﻟﺴﮭﻠﺔ ﻟﺘﻌﯿﯿﻦ ﺷ ﺪة اﻟﺮﺑ ﻮ اﻟﺸ ﻌﺒﻰ ﻛﻤ ﺎ أن
ﺗﻌﯿﯿﻦ ﻧﺴﺒﺔ اﻹﻧﺘﺮﻟﻮﻛﯿﻦ ﻓﻰ اﻟﺪم ﻣﻦ اﻟﺘﺤﺎﻟﯿﻞ اﻟﺴﮭﻠﺔ واﻟﺪﻗﯿﻘﺔ اﻟﺘﻰ ﺗﺴﺎﻋﺪ ﻋﻠ ﻰ اﻟﺘﺸ ﺨﯿﺺ واﻟﺘﻨﺒ ﻮء ﺑﺸ ﺪة
اﻟﺮﺑﻮ اﻟﺸﻌﺒﻰ.