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Role of conformational and linear epitopes in the achievement of tolerance in cow's milk allergy


Kirsten Beyer, Division of Paediatric Allergy & Immunology, Box-No. 1198, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029–6574, USA. E-mail:


Background Cow's milk (CM) is one of the leading causes of food allergy in children. However, approximately 85% of milk-allergic children become clinically tolerant to CM within the first 3 years of life. The mechanisms involved in the achievement of tolerance remain unknown.

Objective To study whether IgE antibodies from children with persistent cow's milk allergy (CMA) differ from children who become clinically tolerant in their ability to recognize linear and conformational epitopes of αs1- and β-casein.

Methods Thirty-six milk-allergic children were included in the study: 11 of the children became clinically tolerant, and 25 had persistent CMA. Blood was obtained from all patients during the time they showed clinical reactions to milk challenge. Six non-milk-allergic children served as controls. Specific IgE antibodies against linear (denatured) as well as conformational (native) milk proteins were determined by probing dot-blots with patients' sera. In addition, selected decapeptides from αs1- and β-casein, previously found to be suggestive of persistent CMA, were synthesized on a cellulose-derivatized membrane and probed with individual sera from 10 patients who outgrew CMA and from 10 patients with persistent CMA.

Results Analysis of immunodot-blots showed that, in comparison to tolerant patients, milk-allergic children with persistent symptoms had a significantly higher ratio of specific IgE antibodies to linearized than to native α- and β-casein (P < 0.005 and P < 0.02, respectively). Comparing the selected decapeptides, six of the 10 patients with persistent allergy recognized the peptide corresponding to amino acids 69–78 from αs1-casein while none of the patients who outgrew CMA had IgE binding to this epitope.

Conclusion Patients with persistent milk allergy possess higher detectable levels of IgE antibodies to linear epitopes from αs1- and β-casein than children who have achieved tolerance. Specific IgE binding to particular linear epitopes in αs1-casein may be a predictive factor for persistence of CMA.