Allergen-specific basophil suppression associated with clinical tolerance in patients with milk allergy

Abstract

Children with milk allergy who tolerate heat-denatured milk (HM) have less severe reactions and outgrow the condition earlier than those who react to HM, which might be related to differences in IgE-dependent effector cell function. We sought to apply a novel assay to test the hypothesis that HM-tolerant children have suppressed IgE-mediated basophil responses. Allergic, HM-tolerant, outgrown, or control subjects were defined based on oral food challenges. Whole blood cells were stimulated in vitro with a range of milk allergen doses in the presence or absence of autologous serum or with dilutions of autologous serum. Activated basophils were identified by means of flow cytometry as CD63(bright)CD123+CD203c+HLA-DR(-)CD41a(-). HM-tolerant subjects' basophils were significantly less responsive to milk allergen stimulation at all doses than were basophils from HM-reactive (allergic) individuals. In the absence of autologous serum, HM-tolerant subjects' basophils were significantly more reactive at low allergen concentrations. To a lesser extent, autologous serum also inhibited IL-3- and anti-IgE-induced, but not N-formyl-methionyl-leucyl-phenylalanine-induced, responses. The allergen-specific responsiveness of HM-tolerant subjects' basophils increased with dilution of autologous serum with normal pooled serum. Children with milk allergy with a favorable prognosis have evidence of extrinsically suppressed allergen-specific effector cell reactivity.