Epigenetic Features of FoxP3 in Children With Cow's Milk Allergy
Condition: Cow's Milk Allergy
MeSH terms: Hypersensitivity; Milk Hypersensitivity
Study type: Observational

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.
    


Intervention name(s): Extensively hydrolyzed casein formula plus LGG
Intervention type(s): Dietary Supplement
Intervention MeSH terms: Caseins
Observational model: Case-Crossover
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        IgE-mediated CMA children (aged 3 to 18 months) consecutively referred to the tertiary
        Pediatric Allergy Center for oral food challenge.

        During the same study period, consecutive healthy children, not at risk of atopic disorders
        (namely, those without a first-degree relative affected by an atopic disorder), attending
        the Center because of minimal surgical procedures served as a control group.

        A venous blood sample (4 ml) was obtained from all patients after oral challenge.