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 beta- and kappa -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 beta- and kappa -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 beta- and kappa -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 beta -casein. Eight major IgE-binding epitopes, as well as two major and two minor IgG-binding epitopes, were detected on kappa -casein. Three of the IgE binding regions on beta -casein and six on kappa -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 beta- and kappa -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.