Background:
The immunopathogenesis of cow's milk protein allergy (CMA) is based on different mechanisms related to immune recognition of protein epitopes, which can be affected by industrial processing.
Purpose of this Diagnosis and RAtionale against Cow’s Milk Allergy (DRACMA) guidelines update III paper¹ is to give an overview of milk protein allergens on a molecular basis, to review their immunogenicity and allergenicity in the context of industrial processing, in order to improve the understanding of IgE-mediated, mixed and non-IgE mediated hypersensitivities to CMA.

Results:
Raw cow´s milk from farms has been associated with protection against allergies, asthma and atopic sensitization. This has recently been associated with the native whey proteins, like α-lactalbumin, β-lactoglobulin, bovine immunoglobulins or serum albumins, as well as with their lipophilic ligands. To facilitate safe and large-scale marketing, milk has to undergo industrial processing involving multiple technical steps, like acidic treatment, heating, filtration and defatting, sometimes irradiation, microwave treatment, drying, hydrolyzation and more. Milk processing results in structural changes of its proteins, like linearization, fragmentation, occurrence of homo- and oligomeric complexes and of larger aggregates. While some epitopes are lost, neoepitopes are newly generated and aggregated proteins also have a higher immunogenicity. Also, immunomodulatory lipophilic compounds in the milk matrix are separated during defatting.

Conclusion:
While unprocessed, fresh cow´s milk contains various tolerogenic factors, these are impaired by industrial processing. As a result, industrially processed milk harbours a higher allergenicity, supporting the spectrum of immunopathogenic mechanisms underlying CMA. Further studies are warranted to understand how to prevent turning milk protein compounds into allergens.