|Year : 2019 | Volume
| Issue : 4 | Page : 240-244
To evaluate total serum immunoglobulin E level and factors that effect on this level in Iraqi asthmatic children
Raghdah Maytham Hameed1, Mohanad Mohsin Ahmed1, Haidar Abdul Amir Najim Abood2, Aqeel Mahdi Hussein3
1 Department of Medical Microbiology, University of Kerbala, Karbala, Iraq
2 Department of Pharmacology, University of Kerbala, Karbala, Iraq
3 Department of Consultant Pediatrician, Karbala Teaching Hospital for Children, Karbala, Iraq
|Date of Submission||25-Aug-2019|
|Date of Acceptance||31-Oct-2019|
|Date of Web Publication||03-Dec-2019|
Ms. Raghdah Maytham Hameed
Department of Medical Microbiology, University of Kerbala, Karbala
Source of Support: None, Conflict of Interest: None
Background: Immunoglobulin E (IgE) has an important role in allergic disease, especially in asthma because it is highly responsive to the allergens; hence, the measure of IgE levels helps in the diagnosis of asthma and monitoring the patient state. Methods: The 85 asthmatic children, including 59 males and 26 females with asthma who had ages between 1 and 16 years collected at Karbala Teaching Hospital for Children with healthy controls which have same age and gender, were measured total IgE levels for them by using EUROIMMUN IgE ELISA kit. The clinical characteristics of patients were recorded by questionnaire and measurement of absolute eosinophil count by peripheral blood smear. Results: There was highly significantly different in IgE levels between patients and controls (P < 0.001). High IgE level observed in 42 (49.4%) of asthmatic patients was relating to age, eosinophil count, exposure to cigarette smoke, the severity of asthma, and use of treatment. Conclusions: Total serum IgE has an important role in the diagnosis of asthma and there are many factors affect its levels in asthmatic patients.
Keywords: Absolute eosinophil count, asthma severity, bronchial asthma, total serum immunoglobulin E
|How to cite this article:|
Hameed RM, Ahmed MM, Abood HA, Hussein AM. To evaluate total serum immunoglobulin E level and factors that effect on this level in Iraqi asthmatic children. Biomed Biotechnol Res J 2019;3:240-4
|How to cite this URL:|
Hameed RM, Ahmed MM, Abood HA, Hussein AM. To evaluate total serum immunoglobulin E level and factors that effect on this level in Iraqi asthmatic children. Biomed Biotechnol Res J [serial online] 2019 [cited 2019 Dec 9];3:240-4. Available from: http://www.bmbtrj.org/text.asp?2019/3/4/240/272186
| Introduction|| |
Asthma is one of the most common chronic, noncommunicable diseases in children and adults. It is a common condition due to chronic inflammation of the lower respiratory tract. It features variable airway obstruction and bronchial hyperresponsiveness. Characterized by episodic or persistent symptoms of wheezing, dyspnea, and cough. If an allergic trigger is suspected, an allergy diagnosis consisting of medical history and/or definition of the immunoglobulin E (IgE) should be performed.
IgE is a type of antibody produced by plasma cells located in lymph nodes draining the site of antigen entry or locally, at the sites of allergic reactions, by plasma cells derived from germinal centers developing within the inflamed tissue. IgE is pathogenic in allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy.
The pathogenic role of IgE antibodies in triggering and maintaining allergic inflammation in response to allergens is due to the binding of multivalent allergens to allergen-specific IgEs on sensitized effector cells. These interactions trigger effector cell activation, resulting in the release of potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. Hence, the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Further, the elevated level of total serum IgE may demonstrate the allergic etiology of asthma in the subjects studied.
In some studies, asthmatic children with higher asthma severity have a higher serum concentration of total IgE., While allergy symptoms may precede elevated specific IgE or represent a different pathway to asthma. However, the role of IgE in allergic asthma is still a matter of debate. Total IgE increased with age, but allergen-specific IgE levels significantly decreased with age, with a trend specific for each allergen tested. Furthermore, IgE levels were higher in boys and differed across age groups in boys and girls. Total IgE exhibits sexual dimorphism in humans (with males demonstrating higher IgE than females). The elevated levels of IgE to some of the common environmental allergens suggests an important role of atopy in the expression of asthma in this developing country's urban setting. Differences in total IgE levels and specific allergen sensitization are likely a result of the complex interplay between exposures associated with socioeconomic disadvantage. It is influenced by exposure to passive smoking, pollen, cold, and pets and is associated with blood eosinophilia.,
The presence of an IgE-mediated allergic reaction in patients with asthma is often related to a family history of the disease. In conclusion, total serum IgE was found to be significantly associated with the age, exposure to cigarette smoke, and raised eosinophil count in asthmatic children.
The study protocol was approved by the ethical committee in the Karbala Health Directorate. In addition, verbal approval was taken from the patients and/or their parents before taking the sample. Health measures and safety were taken when sampling.
| Methods|| |
This study included a total of 85 consecutive asthmatic children (59 males and 26 females) attending the Asthma Clinic at Karbala Teaching Hospital for Children in the period extending from October 2018 to December 2018. All children had the American Thoracic Society criteria for asthma. In this study, 36 of asthmatic children had visited the clinic regularly and receiving regular treatment with either inhaled corticosteroids (ICSs) or Montelukast, whereas 49 of them were newly diagnosed. Their ages were ranged between 1 and 16 years. The control groups included 85 children (53 males and 32 females) with the same ages and sex of the patients were randomly selected from the hospitals and the local community.
Sample collection and processing
Serum and whole blood were collected from each participant sera were used to determine total serum IgE levels by BioTek ELx 800 automated immunoassay analyzer (BioTek, USA) using EUROIMMUN total IgE ELISA kit (LOT NO. A180417AC). While whole blood was used for total and differential white blood cells (WBCs) count were measured using Sysmex XN-350 five differential automated hematology analyzer (Sysmex, Japan). Differential leukocyte count was displayed in percentage. Therefore, the absolute eosinophil count was measured by the following equation: Absolute Eosinophil Count = (WBC × Eosinophils %)/100
Data were introduced into a specific software Statistical Package for the Social Sciences version 21 for Windows (GraphPad Software, San Diego, California, USA) to do statistical analysis, while the figures constructed was by EXCEL program of Microsoft Office 2010 (GraphPad prism Microsoft).
The results were expressed as mean ± standard deviation comparisons between two mean were performed using t-test, whereas ANOVA was using to compare among mean. A value of P < 0.05 was considered to indicate the statistical significance and highly significant if P < 0.001. Chi-square used to compare between two categorical variables.
| Results|| |
[Table 1] shows the demographic and biochemical profile of asthmatics and nonasthmatic children. Clinical characteristics of asthmatic participants between an elevated level of total serum IgE and normal IgE level are presented in [Table 2]. The results showed no significant associations of gender, age, height, weight, and body mass index between the asthmatic patients and healthy controls. While there was a highly significant difference of absolute eosinophil count, total serum IgE, and family history of asthma/allergic diseases between them P > 0.001, as shown in [Table 1].
|Table 1: Demographic and biochemical profile of asthmatic and nonasthmatic groups|
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|Table 2: Comparison of demographic characteristics between asthmatic children with high-level immunoglobulin E and normal level of immunoglobulin E|
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It was observed that 42 (49.4%) from 85 asthmatic patients have high total serum IgE. The mean of total serum IgE levels for + ve IgE (≥100 IU/mL) asthmatic children were 344.03 ± 215.9 IU/ml and for − ve IgE (<100 IU/mL) patients were 38.7 ± 28.2 IU/mL.
Furthermore, in this study, there was a significant difference in age, severity of asthma, exposure to cigarette smoke, absolute eosinophil count, and use of treatment between the elevated levels of total serum IgE in asthmatics patients compared to asthmatic patients who have normal levels of total serum IgE, shown in [Table 2]. On the other hand, there was no effect of the family history of asthma/allergic diseases on IgE levels as shown in [Figure 1] (P = 0.466). In [Figure 2], there was a significant difference in total serum IgE between mild and moderate asthmatic children (P = 0.049).
|Figure 1: Difference between family history of allergic disease in mean of total serum immunoglobulin E|
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|Figure 2: The mean of total serum immunoglobulin E between mild and moderate asthmatic children. *: Significant (P < 0.05)|
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| Discussion|| |
The present study showed elevated total serum IgE (≥100 IU/ml) in 49.4% of asthmatic children. In addition, there was a highly significant difference between asthmatic and healthy controls in IgE level (P< 0.001). The result agrees with previous studies in Iraq, Haidar A. N. Abood, who mentioned that 48.7% of patients showed positive IgE screening test and 51.3% of patients showed negative IgE screening test. Ahmad Al Obaidi et al. indicate that mean serum IgE level was 554 IU/ml in asthmatic patients, while that of the control was 69 IU/ml. Further, the present results agree with previous international study, where Strømgaard et al. found a strong positive relationship between total serum IgE levels and asthma in children. Increases in IgE levels could be viral (which is the most common cause of exacerbation of symptoms in asthma) or allergen-specific or could simply represent a generalized upregulation of IgE production. Thus, IgE levels may be used to differentiate between asthmatic and nonasthmatic individuals.,
The current study showed that the prevalence of atopy in asthmatic children is increased with age. In which the higher IgE level was present in 7.14% of patients aged <2 years, 21.4% of patients aged 2–5 years, and 54.76% of population at school age (5–10 years), this data similar to other previous studies, which mentioned that when the age of asthmatic patients is considered, the IgE levels are greatly affected.
This study observed that male gender was predominant in both high IgE level and normal IgE level asthmatic children, and there was nonsignificant association between IgE level and gender, which agree with another study. This result because childhood asthma was reported to be more prevalent in boys than in girls.
Exposure to tobacco smoking was the most environmental factor cause the trigger of asthma and an increase of IgE levels.,, This study found that 47% of patients who exposure to smoking had high IgE level, while only 32% of them had normal IgE level.
In spite of some evidence suggesting the relationship between living in urban and increase of IgE levels, but the study showed asthmatic patients who lived urban was dominated at both high and normal IgE level, due to an increasing prevalence of asthma among children who lived in the urban area compared to children who lived in a rural area.
In the present study, it was observed that high absolute eosinophils count (≥400 cell/mm3) for patients in high IgE group was 57% higher than that for patients in normal IgE group (39.5%), and there was a highly significant difference (P< 0.001). This result agrees with other previous study,,, who mentioned that there was a positive relation of total IgE and total eosinophil count in allergic diseases.
Further, the data showed that 52.38% of asthmatic patients on controller therapy had high IgE level. This result is consistent with the previous results, who said that the IgE level in the treated asthmatic patients was significantly higher than that in the asthmatic controls. Other previous study mentioned that only high doses of ICSs and montelukast decreased the serum IgE levels in asthmatic patients. These result because of the montelukast action in asthmatic children which act by reduced interleukin (IL)-4 and IL-5 but increased of transferrin (TFN)-γ. Further, TFN-γ can inhibit the IL-4, induced high expression of IgE, and the occurrence of an allergic reaction.
The present study showed 207.5 IU/ml of total serum IgE in moderate asthmatic children, while 164.3 IU/ml of total serum IgE in mild asthmatic children, this result agrees with another study such as Borish, who mentioned that 145.8 IU/ml mean of IgE levels in moderate asthmatic children while 137.8 IU/ml of total serum IgE in mild asthmatic children. In addition, Kovac found 156.2 kIU/L of IgE levels in mild asthma and 288.0 kIU/L IgE in moderate asthma. Sandeep who found that levels of IgE increased as the severity of asthma increased. In contrast, Davila showed increase of total serum IgE in both mild and moderate asthma, whereas no differences between them. The increase of IgE levels in mild and moderate asthma because IgE binds to high-affinity receptors on effector cells, such as basophils and mast cells. Then, allergen binds to IgE and initiates an inflammatory cascade, resulting in the release of proinflammatory mediators that contribute to the acute and chronic symptoms of asthma and allergic airway diseases.
The study found that there was a highly associated between positive family history of asthma/allergic disease and asthma in children, 89.4% of asthmatic children had a family history of asthma, but there was no effect of this factor on the level of IgE, these results agree with Abood et al.
| Conclusions|| |
IgE plays an important role in the diagnosis of asthma and there are many factors effect on the IgE level in asthmatic children such as age, eosinophil count, exposure to cigarette smoke, and asthma severity.
We are thankful to the specialist doctors hematologist at Al-Sader hospital in AL-Najaf/Iraq (Dr. Thulfiqar Azeez Arab and Dr. Mohammed Abd Allah AL-Mosawi) for providing a helping in the examination of peripheral blood smear.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet 2018;391:783-800.
Mims JW. Asthma: Definitions and pathophysiology. Int Forum Allergy Rhinol 2015;5 Suppl 1:S2-6.
McCracken JL, Veeranki SP, Ameredes BT, Calhoun WJ. Diagnosis and management of asthma in adults: A review. JAMA 2017;318:279-90.
Horak F, Doberer D, Eber E, Horak E, Pohl W, Riedler J, et al.
Diagnosis and management of asthma statement on the 2015 GINA guidelines. Wien Klin Wochenschr 2016;128:541-54.
Janeway CA Jr., Travers P, Walport M, Shlomchik MJ. Immunobiology: The Immune System in Health and Disease. The Production of IgE. 5th
ed. New York: Garland Science; 2001.
Wu LC, Scheerens H. Targeting igE production in mice and humans. Curr Opin Immunol 2014;31:8-15.
Karagiannis SN, Karagiannis P, Josephs DH, Saul L, Gilbert AE, Upton N, et al.
Immunoglobulin E and allergy: Antibodies in immune inflammation and treatment. Microbiol Spectr 2013;1.
Platts-Mills TA, Schuyler AJ, Erwin EA, Commins SP, Woodfolk JA. IgE in the diagnosis and treatment of allergic disease. J Allergy Clin Immunol 2016;137:1662-70.
Lama M, Chatterjee M, Chaudhuri TK. Total serum immunoglobulin e in children with asthma. Indian J Clin Biochem 2013;28:197-200.
Kovac K, Dodig S, Tjesić-Drinković D, Raos M. Correlation between asthma severity and serum igE in asthmatic children sensitized to dermatophagoides pteronyssinus. Arch Med Res 2007;38:99-105.
Naqvi M, Choudhry S, Tsai HJ, Thyne S, Navarro D, Nazario S, et al.
Association between igE levels and asthma severity among African American, Mexican, and puerto rican patients with asthma. J Allergy Clin Immunol 2007;120:137-43.
Rotsides DZ, Goldstein IF, Canfield SM, Perzanowski M, Mellins RB, Hoepner L, et al.
Asthma, allergy, and igE levels in NYC head start children. Respir Med 2010;104:345-55.
Silvestri M, Pistorio A, Battistini E, Rossi GA. IgE in childhood asthma: Relevance of demographic characteristics and polysensitisation. Arch Dis Child 2010;95:979-84.
De Amici M, Ciprandi G. The age impact on serum total and allergen-specific igE. Allergy Asthma Immunol Res 2013;5:170-4.
Haselkorn T, Szefler SJ, Simons FE, Zeiger RS, Mink DR, Chipps BE, et al.
Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR. Pediatr Allergy Immunol 2010;21:1157-65.
Raby BA, Soto-Quiros ME, Avila L, Lake SL, Murphy A, Liang C, et al.
Sex-specific linkage to total serum immunoglobulin E in families of children with asthma in costa rica. Hum Mol Genet 2007;16:243-53.
Ige OM, Falade AG, Arinola OG. Atopy is a risk factor for adult asthma in urban community of South Western Nigeria. Lung India 2012;29:114-9. [Full text]
Litonjua AA, Celedón JC, Hausmann J, Nikolov M, Sredl D, Ryan L, et al.
Variation in total and specific igE: Effects of ethnicity and socioeconomic status. J Allergy Clin Immunol 2005;115:751-7.
Satwani H, Rehman A, Ashraf S, Hassan A. Is serum total igE levels a good predictor of allergies in children? J Pak Med Assoc 2009;59:698-702.
Kim YS, Kim HY, Ahn HS, Sohn TS, Song JY, Lee YB, et al.
The association between tobacco smoke and serum immunoglobulin E levels in korean adults. Intern Med 2017;56:2571-7.
Mitsunobu F, Mifune T, Hosaki Y, Ashida K, Tsugeno H, Okamoto M, et al.
IgE-mediated and age-related bronchial hyperresponsiveness in patients with asthma. Relationship to family history of the disease. Age Ageing 2000;29:215-20.
Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al.
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43:343-73.
Abood HA, Ghazal MR, Al-Musawi ZM. Total serum IgE level in relation to some risk factors of childhood asthma. Karbala J Pharm Sci 2013; p. 78-84.
Ahmad Al Obaidi AH, Mohamed Al Samarai AG, Yahya Al Samarai AK, Al Janabi JM. The predictive value of igE as biomarker in asthma. J Asthma 2008;45:654-63.
Strømgaard S, Thomsen SF, Fenger M, Backer V. Predictors of serum total igE in a random sample of 7-17 year old children. ISRN Allergy 2011;2011:169859.
Corne JM, Holgate ST. Mechanisms of virus induced exacerbations of asthma. Thorax 1997;52:380-9.
Sandeep T, Roopakala MS, Silvia CR, Chandrashekara S, Rao M. Evaluation of serum immunoglobulin E levels in bronchial asthma. Lung India 2010;27:138-40.
] [Full text]
Gergen PJ, Arbes SJ Jr., Calatroni A, Mitchell HE, Zeldin DC. Total igE levels and asthma prevalence in the US population: Results from the national health and nutrition examination survey 2005-2006. J Allergy Clin Immunol 2009;124:447-53.
Yao TC, Ou LS, Yeh KW, Lee WI, Chen LC, Huang JL, et al.
Associations of age, gender, and BMI with prevalence of allergic diseases in children: PATCH study. J Asthma 2011;48:503-10.
Almqvist C, Worm M, Leynaert B, Working group of GA2LEN WP 2.5 Gender. Impact of gender on asthma in childhood and adolescence: A GA2LEN review. Allergy 2008;63:47-57.
Oryszczyn MP, Annesi-Maesano I, Charpin D, Paty E, Maccario J, Kauffmann F, et al.
Relationships of active and passive smoking to total igE in adults of the epidemiological study of the genetics and environment of asthma, bronchial hyperresponsiveness, and atopy (EGEA). Am J Respir Crit Care Med 2000;161:1241-6.
Ciaccio CE, Gentile D. Effects of tobacco smoke exposure in childhood on atopic diseases. Curr Allergy Asthma Rep 2013;13:687-92.
Gern JE. The urban environment and childhood asthma study. J Allergy Clin Immunol 2010;125:545-9.
Koh HS, Lee KS, Han DH, Rha YH, Choi SH. Relationship between serum total IgE, specific IgE, and peripheral blood eosinophil count according to specific allergic diseases. Allergy Asthma Respir Dis 2013;1:123-8.
Sacco O, Sale R, Silvestri M, Serpero L, Sabatini F, Raynal ME, et al.
Total and allergen-specific igE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites. Pediatr Allergy Immunol 2003;14:475-81.
Kumar RM, Pajanivel R, Koteeswaran G, Menon SK, Charles PM. Correlation of total serum immunoglobulin E level, sputum, and peripheral eosinophil count in assessing the clinical severity in bronchial asthma. Lung India 2017;34:256-61.
] [Full text]
Qu X, Chen Y, Yin C. Effect of montelukast on the expression of CD4+CD25+regulatory T cells in children with acute bronchial asthma. Exp Ther Med 2018;16:2381-6.
Stelmach I, Bobrowska-Korzeniowska M, Majak P, Stelmach W, Kuna P. The effect of montelukast and different doses of budesonide on igE serum levels and clinical parameters in children with newly diagnosed asthma. Pulm Pharmacol Ther 2005;18:374-80.
Borish L, Chipps B, Deniz Y, Gujrathi S, Zheng B, Dolan CM, et al.
Total serum igE levels in a large cohort of patients with severe or difficult-to-treat asthma. Ann Allergy Asthma Immunol 2005;95:247-53.
Davila I, Valero A, Entrenas LM, Valveny N, Herráez L; SIGE Study Group. et al.
Relationship between serum total igE and disease severity in patients with allergic asthma in spain. J Investig Allergol Clin Immunol 2015;25:120-7.
Hamelmann E. The rationale for treating allergic asthma with anti-IgE. Eur Respir Rev 2007;16:61.
[Figure 1], [Figure 2]
[Table 1], [Table 2]