Epigenetic Features of FoxP3 in Children With Cow's Milk Allergy

Cow's Milk Allergy Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02779881
• Other study ID #: 1-14
• Status: Completed
• Phase: N/A
• First received: May 16, 2016
• Last updated: May 19, 2016
• Start date: December 2012
• Est. completion date: April 2014

Study information

• Verified date: May 2016
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Observational

Clinical Trial Summary

Epigenetic mechanisms have been implicated in the pathogenesis of food allergy. The investigators previously demonstrated that tolerance acquisition in children with Immunoglobulin E- (IgE) mediated cow's milk allergy (CMA) is driven by epigenetic modulation of the Th1 and Th2 cytokine genes. A regulatory T cell (Treg) suppressive phenotype, characterized by stable expression of the transcription factor "Forkhead box Protein 3" (FoxP3), plays a pivotal role in food tolerance. FoxP3 mRNA expression is lower in children with atopic asthma or IgE-mediated food allergy than in healthy children. FoxP3 stable expression requires full CpG demethylation of its transcriptional regulatory regions, and, moreover, hypermethylation of the FoxP3 gene has been associated with reduced Treg function and allergy.

DNA methylation is a biologically and chemically stable epigenetic modification that locks in long-term gene expression patterns. The demethylation status of FoxP3 at a highly conserved region within the Treg-specific-demethylated-region (TSDR), a CpG-rich, located on the 2nd conserved non-coding sequence of FoxP3 (CNS2), is restricted to Tregs. Transcriptional activity of the TSDR is essentially determined by its methylation status : it is completely inactive in its methylated state, but when the TSDR is demethylated, transcription factors such as Ets-1 and Creb can bind to the TSDR. TSDR demethylated and open chromatin conformation in the Foxp3 locus leads to stable phenotype differentiated Foxp3+ Treg. FoxP3 TSDR demethylation in peripheral blood mononuclear cells (PBMCs) has been associated with reduced atopic sensitization and asthma in children. Epigenetic regulation of antigen-induced T-cell subsets may predict a state of immune tolerance in food allergy. Indeed, DNA methylation of the FoxP3 gene in Tregs decreased during oral tolerance acquisition in patients with peanut allergy undergoing oral immunotherapy. The aim of this study was to evaluate further the epigenetic regulation of FoxP3 gene in children with IgE-mediated CMA.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 18 Months

Eligibility

Inclusion Criteria:

• IgE-mediated CMA children (aged 3 to 18 months)

Exclusion Criteria:

• allergic disorders or food allergies other than cow's milk allergy

• eosinophilic disorders of the gastrointestinal tract

• food protein-induced enterocolitis syndrome

• concomitant chronic systemic diseases

• congenital cardiac defects

• active tuberculosis

• autoimmune diseases

• immunodeficiency

• chronic inflammatory bowel diseases

• celiac disease

• cystic fibrosis

• metabolic diseases

• lactose intolerance

• malignancy

• chronic pulmonary diseases

• malformations of the gastrointestinal tract

Study Design

Observational Model: Case-Crossover, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Cow's Milk Allergy
• Milk Hypersensitivity

Intervention

Dietary Supplement:
• Extensively hydrolyzed casein formula plus LGG

Locations

Country	Name	City	State
Italy	University of Naples Federico II	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA demethylation (rate, in %) of the Treg-specific-demethylated-region (TSDR) of FoxP3		At enrollment	No