IgE and IgG Binding Epitopes on α-Lactalbumin and β-Lactoglobulin in Cow’s Milk Allergy

Abstract

Background: Cow’s milk is one of the most common causes of food allergy in the first years of life. We recently defined IgE and IgG binding epitopes for α_s1-casein, a major cow’s milk allergen, and found an association between recognition of certain epitopes and clinical symptoms of cow’s milk allergy (CMA). Since α-lactalbumin (ALA) and β-lactoglobulin (BLG) are suspected to be significant allergens in cow’s milk, we sought to determine the structure of sequential epitopes recognized by IgE antibodies to these proteins. We further sought to assess the pattern of epitope recognition in association with the clinical outcome of CMA. Methods: According to the known amino acid sequence of ALA and BLG, 57 and 77 overlapping decapeptides (offset by two amino acids), respectively, were synthesized on a cellulose derivatized membrane. Sera from 11 patients 4–18 years of age with persistent CMA (IgE to cow’s milk >100 kU_A/l) were used to identify IgE binding epitopes. In addition, 8 patients <3 years of age and likely to outgrow their milk allergy (IgE to cow’s milk <30 kU_A/l) were used to investigate the differences in epitope recognition between patients with ‘persistent’ and those with ‘transient’ CMA. Seven patients 4–18 years of age were used for assessing the IgG binding regions. Results: In patients with persistent allergy, four IgE binding and three IgG binding regions were identified on ALA, and seven IgE and six IgG binding epitopes were detected on BLG. The younger patients that are likely to outgrow their allergy recognized only three of these IgE binding epitopes on BLG and none on ALA. Conclusions: The presence of IgE antibodies to multiple linear allergenic epitopes may be a marker of persistent CMA. The usefulness of IgE binding to distinct epitopes on whey proteins in defining the patients that would have a lifelong CMA needs to be investigated in further studies.

A Recombinant Hypoallergenic Parvalbumin Mutant for Immunotherapy of IgE-Mediated Fish Allergy

“…IgE epitopes of Cyp c 1, a prominent class I food allergen, capable of inducing severe systemic anaphylactic reactions, thus seem to be of the conformational type. In case of other class I food allergens, which frequently elicit life-threatening anaphylactic reactions, such as the major peanut allergens Ara h 1, Ara h 2, and Ara h 3 (32-34), the major shrimp allergen, Pen a 1 (35), and major milk allergens (36,37), it has been reported that IgE-binding primarily occurs to linear epitopes (reviewed in Ref. 12).…”

Bioactivity of β-lactoglobulin and α-lactalbumin—Technological implications for processing

“…In patients likely to 512 outgrow their allergy, three of these IgE-binding epitopes were detected on β-lg and none on α-la 513 (Järvinen et al, 2001). A proteomics approach in combination with immunoblotting, indicated 514 that all major milk proteins including β-lg were allergens, though no evidence was found for α-la 515 (Natale et al, 2004).…”

Potential, pitfalls, and prospects of food allergy diagnostics with recombinant allergens or synthetic sequential epitopes

“…[10], [120], [121], [122] and [123] [124], [125], [126], [127], [128], [129] and [130] However, other studies at different shifting offsets, with different peptides sizes, or both revealed different sets of immunodominant sequential epitopes for the same allergens. [29], [124], [125], [126], [127], [130] and [131] Nevertheless, approaches to use these alleged immunodominant peptides for the risk assessment of life-threatening symptoms, as well as the prediction of persistence in food hypersensitivity, were apparently successful.…”