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

Background Cow's milk (CM) is one of the leading causes of food allergy in children. However, approximately 85% of milk-allergic children become clini cally tolerant to CM within the first 3 years of life. The mechanisms invol ved 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 i n their ability to recognize linear and conformational epitopes of alpha (s 1)- and beta -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 reactio ns to milk challenge. Six non-milk-allergic children served as controls. Sp ecific 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 alpha (s1)- and beta -casein, previously found to be suggestive of persistent CMA, were synthesized on a cellulose-derivatized membrane and probed with individual sera from 10 pat ients 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 significant ly higher ratio of specific IgE antibodies to linearized than to native alp ha- and beta -casein (P < 0.005 and P < 0.02, respectively). Comparing the selected decapeptides, six of the 10 patients with persistent allergy recog nized the peptide corresponding to amino acids 69-78 from alpha (s1)-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 alpha (s1)- and beta -case in than children who have achieved tolerance. Specific IgE binding to parti cular linear epitopes in alpha (s1)-casein may be a predictive factor for p ersistence of CMA.