Oral Food Desensitization in Children With IgE-Mediated Cow's Milk Allergy: Immunological Changes Underlying Desensitization

PURPOSE: This study aimed to evaluate the safety and efficacy to induce clinical desensitization to cow's milk (CM) of an oral immunotherapy (OIT) protocol in a pediatric population with cow's milk allergy (CMA). In addition, the immune responses against β-casein, of peripheral blood mononuclear cells (PBMCs) from CMA patients, before and after the protocol were evaluated and compared to a nonallergic population. METHODS: A group of 20 children with IgE-mediated CMA and 15 nonallergic children were recruited. Allergic subjects underwent an OIT protocol based on weekly doses of commercial semi-skimmed ultra-high temperature treated (UHT) CM, followed by a maintenance phase. Immune profiles and changes in all subjects were investigated by measuring Th1, Th2, and Treg cytokines, transcription factors, and specific IgE and IgG4 levels. RESULTS: The CM-OIT protocol enabled to desensitize 70% of the allergic patients. Successful OIT was accompanied by significant increases in casein-specific IgG4 levels, together with a reduction in the concentration of antigen-specific IgE and in IL-5, IL-13, and IL-10 production by β-casein-stimulated PBMCs. Baseline significant differences observed between allergic and nonallergic children in IL-13 and IL-5 levels were no longer found once the protocol had finished. CONCLUSIONS: The OIT protocol was safe and effective in inducing milk desensitization in 70% of the children with CMA, leading to alterations in their immune profiles toward a nonallergic phenotype.

Antibody Production, Anaphylactic Signs, and T-Cell Responses Induced by Oral Sensitization With Ovalbumin in BALB/c and C3H/HeOuJ Mice

PURPOSE: Two mouse strains, BALB/c and C3H/HeOuJ, broadly used in the field of food allergy, were compared for the evaluation of the allergenic potential of ovalbumin (OVA). METHODS: Sensitization was made by administering 2 different OVA doses (1 and 5 mg), with cholera toxin as Th2-polarizing adjuvant. Antibody levels, severity of anaphylaxis, and Th1 and Th2 responses induced by the allergen were assessed. In addition, because the mice selected had functional toll-like receptor 4, the influence of contamination with lipopolysaccharide (LPS) on the immunostimulating capacity of OVA on spleen cells was also evaluated. RESULTS: Both strains exhibited similar susceptibility to OVA sensitization. The 2 protein doses generated similar OVA-specific IgE and IgG1 levels in both strains, whereas C3H/HeOuJ mice produced significantly more IgG2a. Oral challenge provoked more severe manifestations in C3H/HeOuJ mice as indicated by the drop in body temperature and the severity of the anaphylactic scores. Stimulation of splenocytes with OVA led to significantly higher levels of Th2 and Th1 cytokines in BALB/c, and these were less affected by protein contamination with LPS. CONCLUSIONS: The antibody and cytokine levels induced by OVA in BALB/c mice and the observation that BALB/c spleen cell cultures were more resistant than those of C3H/HeOuJ mice to the stimulus of LPS make this strain prone to exhibit Th2-mediated food allergic reactions and very adequate for the study of the features of OVA that make it allergenic.