Original article
Asthma, lower airway diseases
Decreased FOXP3 mRNA expression in children with atopic asthma and IgE-mediated food allergy

https://doi.org/10.1016/j.anai.2015.08.015Get rights and content

Abstract

Background

The role of T regulatory lymphocytes has been investigated in various allergic diseases. However, the precise relation between the phenotype and severity of allergic diseases and the changes in FOXP3 mRNA expression are not fully understood.

Objective

To compare the expression of FOXP3 mRNA in children with asthma with and without concomitant food allergy (FA) with healthy children and children with only FA.

Methods

The study included 82 children: 15 with atopic asthma and IgE-dependent FA, 27 with atopic asthma without FA, 20 with IgE-dependent FA without asthma, and 20 healthy children without atopy. Reverse transcription was performed using a commercially available High Capacity cDNA Archive Kit (Applied Biosystems, Carlsbad, California). Analysis was carried out with a 7900HT real-time polymerase chain reaction system (Applied Biosystems).

Results

The average level of the FOXP3 gene expression in children with allergy was significantly lower compared with healthy children (2.2 ± 1.3 vs 4.2 ± 4.2; P = .014). The lowest mean level of FOXP3 mRNA expression (1.9 ± 1.6) was recorded in children with asthma and FA, and the highest level (4.2 ± 4.2) was recorded in healthy children without atopy (P = .036). A milder course of asthma or the degree of allergic reaction after a food challenge was associated with higher FOXP3 mRNA expression.

Conclusion

Significantly lower levels of FOXP3 gene expression, observed more commonly in children with asthma and IgE-dependent FA than in healthy controls, were associated with a more severe clinical course. Therefore, FOXP3 expression could serve as an indicator of severe asthma with concomitant atopic conditions such as IgE-dependent FA.

Introduction

Allergic diseases are believed to be a result of an improper equilibrium between allergen-activated CD4+CD25+ T regulatory lymphocytes (Tregs) and T-helper type 2 (TH2) effector cells. The significance of Tregs in the pathogenesis of allergic diseases has not been precisely defined. Although some studies have indicated Treg deficiency or weakening of Treg function in allergic diseases, the outcomes of other studies hae been contradictory.

Numerous recent studies have suggested that Tregs can be determined through the expression of the transcription factor FOXP3 (forkhead box p3), a molecule specific to Tregs.1 FOXP3 is the main gene responsible for the development and function of Tregs.[1], [2] Foxp3 protein silences cytokine promotors, thus inhibiting their expression, through interactions with the nuclear factor of activated T cells, a key transcription factor. FOXP3 is believed to provide a blockade for TH1 and TH2 lymphocytes[3], [4] and to correlate with the regulatory ability of CD4+CD25+ cells.[3], [4], [5]

The role of Tregs has been investigated in various allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. However, it remains unclear whether phenotypes of allergic diseases are associated with different levels of FOXP3 expression and what role FOXP3 plays in the degree of their severity. Although Tregs are recognized to play an important role in asthma pathogenesis and tolerance acquisition,[6], [7], [8] information on their role in food allergy (FA) is scarce and ambiguous. Moreover, despite the growing number of studies suggesting a possible relation between FA and asthma, the nature of this relation has not been fully elucidated and remains controversial.[9], [10] Therefore, the aim of this study was to evaluate the expression of FOXP3 in children with asthma with and without concomitant FA and to compare it with the expression level in healthy children and children with only FA.

Section snippets

Subjects

Children 6 to 18 years old were recruited from patients treated at the Department of Pediatric Allergology, Gastroenterology and Nutrition of the Medical University of Lodz (Lodz, Poland) from January 2010 through December 2013.

The inclusion criteria were children with atopic asthma diagnosed according to Global Initiative for Asthma criteria,11 IgE-mediated FA diagnosed according to European Academy of Allergology and Clinical Immunology recommendations,[12], [13] an elimination diet for at

Results

Eighty-two children participated in the study. The study group consisted of 62 children: 15 with atopic asthma and IgE-mediated FA, 27 with atopic asthma without IgE-mediated FA, and 20 with IgE-mediated FA without asthma. The control group was comprised of 20 healthy children without atopy. The characteristics of the study and control groups are listed in Table 1. The mean FOXP3 mRNA expression level in children with allergy (children with asthma, with asthma and FA, and with isolated FA) was

Discussion

The present study showed that FOXP3 expression was significantly lower in children with allergies (children with asthma, with asthma and concomitant FA, and with isolated FA) compared with healthy children. Although FOXP3 expression was lowest in children with asthma and FA, no significant differences among the remaining children were observed. To the authors' knowledge, this is the first study evaluating FOXP3 expression in children with concomitant asthma and FA.

Prior studies have indicated

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    Disclosures: Authors have nothing to disclose.

    Funding Sources: This study was supported by grant 502-11-750 from the Medical University of Lodz.

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