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 β‐lactoglobulin and α‐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 β‐lactoglobulin at diagnosis (P=0.01), and lower IgG4 levels to β‐lactoglobulin (P=0.04) and α‐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 β‐lactoglobulin‐specific serum IgA at the time of diagnosis, and later increasing specific IgG4 levels to β‐lactoglobulin and α‐casein. Cite this as: E. M. Savilahti, K. M. Saarinen and E. Savilahti, Clinical & Experimental Allergy, 2010 (40) 251–256.