Duration of clinical reactivity in cow's milk allergy is associated with levels of specific immunoglobulin G4 and immunoglobulin A antibodies to β‐lactoglobulin

BACKGROUND: The development of tolerance in IgE-mediated allergies has been associated with lower cow's milk (CM)-specific IgE levels, increasing levels of specific IgG4 and, more contestably, IgA. OBJECTIVE: We investigated whether specific antibody responses to CM proteins differ over time between patients who recovered from cow's milk allergy (CMA) by the age of 3 years and those who developed tolerance only after the age of 8 years. METHODS: The study population comprised of 83 patients with IgE-mediated CMA. They belonged to a cohort of 6209 healthy, full-term infants followed prospectively for the emergence of CMA. Serum samples were available at diagnosis (median age 7 months), 1 year later (median 19 months) and at follow-up (median 8.5 years). Age-matched control subjects with no history of CMA (n=76) participated in the follow-up. Serum levels of IgE antibodies to CM were measured using UniCAP. Levels of IgA, IgG1 and IgG4 antibodies to beta-lactoglobulin and alpha-casein were measured using ELISA. RESULTS: Patients with persistent CMA at the age of 8 years (n=18 at diagnosis, n=16 at later time-points) had higher CM-specific IgE levels at all three time-points (P<0.001) compared with patients who became tolerant by 3 years (n=55 at diagnosis, n=54 a year later, n=40 at follow-up). They had lower serum IgA levels to beta-lactoglobulin at diagnosis (P=0.01), and lower IgG4 levels to beta-lactoglobulin (P=0.04) and alpha-casein (P=0.05) at follow-up. CONCLUSION: High CM-specific IgE levels predict the persistence of CMA. Development of tolerance is associated with elevated levels of beta-lactoglobulin-specific serum IgA at the time of diagnosis, and later increasing specific IgG4 levels to beta-lactoglobulin and alpha-casein.