Characterization of milk-specific immunoglobulins of oral immunotherapy participants

Abstract

Abstract Since the standard treatment for food allergies such as cow’s milk allergy is strict avoidance and epinephrine injection upon anaphylaxis, alternative treatments are needed. Allergic reactions including anaphylaxis are presumed to be due to high-affinity immunoglobulin (Ig)E antibodies against cow’s milk proteins (CMP) such as casein. Currently, our laboratory is leading a pan-Canadian randomized controlled trial of milk oral immunotherapy (OIT). Participants in the OIT receive increasing doses of cow’s milk until 200ml of milk is tolerated without allergic reactions, followed by 12 months of follow-up while continuing to ingest milk and dairy at least twice a week. Using enzyme-linked immunosorbent assay (ELISA) to detect antibodies specific for casein, we determined that female participants have higher casein-specific IgE and IgG4 than male participants. We then aimed to assess whether the sex-dependent change in the affinity of immunoglobulins throughout OIT. Using a modified ELISA that assays for relative binding affinity, we found that the affinity of IgE for casein decreases in approximately half of the participants following the 12-months observation period, compared to the baseline. This is associated with an increase in tolerance and significant protection against minor symptoms or adverse reactions following milk ingestion. The results suggest that oral immunotherapy may induce changes in the affinity binding of allergen-specific IgE and contribute to the improvement of symptoms associated with allergy desensitization to milk.