Improvement in Skin Testing Is Associated with Increases in Milk Component- Specific IgA and IgG4 during Milk Oral Immunotherapy

Rationale: Cow’s milk allergy (CMA) is a frequent cause of severe allergic reactions and anaphylaxis in children. We report on the first randomized controlled trial in Canada evaluating milk oral immunotherapy (OIT) in children. We compared changes in skin prick tests (SPT) between commercial milk extract, fresh milk, and 1:10 diluted fresh milk (fresh milk-1:10) during milk OIT. We also assessed milk-protein specific serum IgE, IgG4, and IgA during milk OIT.

Methods: We performed an interim analysis for the first 9 subjects who completed the escalation phase. SPT to milk extract, fresh milk-1:10, and fresh milk were evaluated at baseline and at 200 ml. Milk protein component (casein, β-lactoglobulin, α-lactalbumin) specific serum IgE, IgG4, and IgA were evaluated at baseline and at 200 ml.

Results: There was a statistically significant decrease in SPT from baseline to 200 ml for milk extract (mean difference 4.44mm, 95% CI 0.01-8.88mm), fresh milk-1:10 (mean difference 6.22mm, 95% CI 1.41- 11.03mm), and fresh milk (mean difference 7.56mm, 95% CI 1.91-13.22mm). In parallel, serum IgG4 and IgA to casein, β-lactoglobulin, and α-lactalbumin significantly increased at 200 ml compared to baseline. Specific IgE to all three milk proteins increased slightly but not significantly. 

Conclusions: Successful escalation phase of milk OIT in IgE-mediated CMA in children is associated with a decrease in milk-specific SPT and an increase in milk protein-components serum IgG4 and IgA.