Epigenetic Effects Involved in Children With Cow's Milk Allergy (EPICMA)
Condition: Cow's Milk Allergy
MeSH terms: Hypersensitivity; Milk Hypersensitivity
Study type: Interventional

Summary: 
      Lactobacillus GG (LGG) is able to exert long lasting effects in children with atopic
      disorders. Nutramigen LGG accelerates tolerance acquisition in infants with cow's milk
      allergy. The mechanisms of these effects are still largely undefined. The effect of LGG could
      be related at least in part by the immunoregulatory role played by LGG. This probiotic can
      balance the generation of cytokines possibly involved in IgE- or non-IgE-mediated cow's milk
      allergy Interleulkin (IL)-4, IL-5, IL-10, IFN-γ , TGF-β, and TNF-Υ), which can contribute to
      modulation of inﬂammatory processes. The investigators have demonstrated that children with
      IgE-mediated CMA produce significantly higher level of IL-4 and IL-13 in response to cow's
      milk protein, and that tolerance is associated with a marked reduction of IL-13 production
      and a concomitant increased frequency of IFN-γ releasing cells.

      Epigenetics studies the heritable (and potentially reversible) changes of the genome
      inherited from one cell generation to the next which alter gene expression but do not involve
      changes in primary DNA sequences, highlighting the complexity of the inter-relationship
      between genetics and nutrition. There are three distinct, but closely interacting, epigenetic
      mechanisms (histone acetylation, DNA methylation, and non-coding microRNAs) that are
      responsible for modifying the expression of critical genes associated with physiologic and
      pathologic processes. The profile of epigenetic modifications associated with Th lineage
      commitment, coupled with the sensitivity of the early developmental period, has led to
      speculation that factors that disrupt these pathways may increase the risk of allergic
      diseases. Specifically, effects on DNA methylation and endogenous histone deacetylase
      inhibitors acting on specific pathways (Th1 and T regulatory cell differentiation) may favour
      Th2-associated allergic differentiation. MicroRNAs are another structural components of an
      epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. It has
      been recently identified a specific Th2-associated microRNA (miR-21) that is critical for the
      regulation of Th cell polarization. It has been previously demonstrated an inverse DNA
      methylation pattern of cytokines involved in Th2 response (IL-4, IL-5) compared with
      cytokines involved in Th1 response (IL-10, INF- y) in children with CMA acquiring oral
      tolerance, with the most pronounced effects in those treated with Nutramigen LGG. The current
      study will prospectively evaluate the effect of Nutramigen LGG and other commercially
      available hypoallergenic formulas on epigenetic mechanisms that may be related to tolerance
      acquisition.
    


Intervention name(s): Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG
Intervention type(s): Dietary Supplement
Intervention description(s): Extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG
Intervention MeSH terms: Caseins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment