Immunologic changes during desensitization with cow's milk: How it differs from natural tolerance or nonallergic state?

Background: Oral immunotherapy (OIT) is a novel allergen-specific treatment for food allergies.

Objective: To investigate the effect of OIT on blocking antibodies, T cell regulation, and cytokine response during immunoglobulin (Ig)E-mediated cow's milk allergy (CMA) treatment.

Methods: A total of 59 children with IgE-mediated CMA who were followed in pediatric allergy outpatient clinic and 18 healthy children were included. The children were evaluated in the following 4 groups: OIT group, elimination group (patients receiving dairy elimination diet), tolerance group (patients who developed tolerance), and healthy control group. Milk-specific IgE, IgG4, and IgA levels, cow's milk induration diameters in skin prick test, CD4 + CD25 + FoxP3 + Treg cell percentages, messenger RNA (mRNA) expressions, and interleukin (IL)-10, transforming growth factor-beta (TGF-β), IL-2, IL-4, and IL-13 cytokine levels were compared between the groups.

Results: The mean age of the patients was 42.6 ± 39 (6-201) months, and 63.6% (n = 49) of the patients were girls. We observed an increase in total IgE levels (P = .02), a decrease in cow's milk sIgE (P = .08, NS), and an increase in cow's milk component (β-lactoglobulin and casein) specific IgA (P < .05) and IgG4 (P < .001) levels at 2 months after the maintenance phase of OIT. In addition, the immune response after OIT treatment, which had a 100% clinical success rate, was notable for similar CD4 + CD25 + FoxP3 + cell percentages (P = .8), and increased IL-10 (P = .04) levels and increased but statistically nonsignificant TGF-β levels (P = .17) compared with those before treatment. FoxP3 mRNA expression was similar to that of patients who developed natural tolerance. Pretreatment and post-treatment FoxP3 mRNA-FoxP3 flow cytometric expressions were positively correlated with TGF-β concentrations in the OIT group.

Conclusion: A successful immune response to OIT was found, possibly through the blockage of IgE-mediated allergen presentation by blocking antibodies, marked IL-10 cytokine response, and TGF-β response. FoxP3 mRNA expression was similar to the natural tolerance mechanism, but more studies are needed.