Role of conformational and linear epitopes in the achievement of tolerance in 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 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 alpha(s1)- 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 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 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 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 alpha- and beta-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 alpha(s1)-casein while none of the patients who outgrew CMA had IgE binding to this epitope.


CONCLUSIONS
Patients with persistent milk allergy possess higher detectable levels of IgE antibodies to linear epitopes from alpha(s1)- and beta-casein than children who have achieved tolerance. Specific IgE binding to particular linear epitopes in alpha(s1)-casein may be a predictive factor for persistence of CMA.
Vila
L
L
Division of Paediatric Allergy and Immunology, The Mount Sinai Medical Center, New York, NY 10029-6574, USA.
Beyer
K
K
Järvinen
K M
KM
Chatchatee
P
P
Bardina
L
L
Sampson
H A
HA
D000293:Adolescent; D000367:Age Factors; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D002648:Child; D002669:Child Welfare; D002675:Child, Preschool; D004311:Double-Blind Method; D000939:Epitopes / Q000009:adverse effects* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology / Q000502:physiology*; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology / Q000378:metabolism; D007223:Infant; D007229:Infant Welfare; D007460:Iodoacetamide / Q000494:pharmacology; D016269:Milk Hypersensitivity / Q000209:etiology* / Q000378:metabolism*; D008894:Milk Proteins / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation / Q000187:drug effects; D011933:Reagent Kits, Diagnostic
D000939:Epitopes; D008894:Milk Proteins; D011933:Reagent Kits, Diagnostic; D007073:Immunoglobulin E; D007460:Iodoacetamide