Identification of IgE and IgG binding epitopes on β- and κ-casein in cow's milk allergic patients

Background: Cow's milk allergy (CMA) affects 2.5% of children aged less than 2 years of age. Although β- and κ-casein are considered among the major allergens responsible for CMA, no data are available on their allergenic epitopes in humans. Objective: The aim of the study was to identify IgE- and IgG-binding epitopes on β- and κ-casein and to determine whether the pattern of epitope recognition is associated with the natural history of CMA. Methods: Overlapping decapeptides representing the entire length of β- and κ-casein, respectively, were synthesized on a cellulose-derivatized membrane. Sera from 15 milk-allergic children, 4-18 years of age, with high levels of specific IgE antibodies to cow's milk were used to identify IgE- and IgG-binding epitopes. In addition, IgE epitopes were screened with pooled or individual sera from younger patients aged less than 3 years and who had low levels of specific serum IgE, who are likely to outgrow CMA. Results: Six major and three minor IgE-binding epitopes, as well as eight major and one minor IgG binding regions, were identified on β-casein. Eight major IgE-binding epitopes, as well as two major and two minor IgG-binding epitopes, were detected on κ-casein. Three of the IgE binding regions on β-casein and six on κ-casein were recognized by the majority of patients in the older age group, but not by the younger patients. Conclusion: Information regarding the immunodominant epitopes in β- and κ-casein may be important for understanding the pathophysiology and natural history of CMA. Differences in epitope recognition may be useful in identifying children who will have persistent milk hypersensitivity.