Molecular Properties of Caseins and Allergenicity

CANDREVA ANGELA; DOCENA, GUILLERMO HORACIO; PETRUCCELLI, SILVANA*

Caseins: Properties, Functions and Health Implications

Nova Science Publishers, Inc.

Lugar: New York; Año: 2016; p. 77 - 102

Cow´s milk allergy (CMA) is an aberrant reaction to the cow´s milk proteins (CMP). CMA is the most frequent cause of food allergy in childhood and several reasons are responsible of the highest prevalence, among them: early introduction of CMP in the infant diet, nature of the cow?s milk (CM) allergens and genetic background. CM has three major allergens: caseins (CAS), α-lactalbumin (ALA) and -lactoglobulin (BLG). There is still controversy about the role of individual CM allergens in primary sensitization and pathogenesis, but CAS are the most frequently IgE recognized CMP. CAS, known as Bos d 8 allergen, is an heterogeneous fraction formed by S1- (Bos d 9), S2- (Bos d 10), - (Bos d 11) and - (Bos d 12) casein. Allergens are recognized as foreign proteins to the host, at this respect S1, - and -CAS have sequence identity degrees with human homologs of 33, 54, 55%, respectively. In contrast, ALA (Bos d 4), BSA (Bos d 6) and lactoferrin (Bos d lactoferrin) sequence identity is over 70%, and proteins with more than 62% of identity are rarely allergic. BLG (Bos d 5) and S2-CAS are absent in human breast milk therefore are highly immunogenic. There is also a causal relationship between resistance to proteolysis and allergenicity. Although isolated caseins are easy degraded, in mammalian milk they are associated in micelles that are resistant to proteolysis. In correlation with this, dephosphorylation destabilizes micelle structure reducing CAS allergenicity. In addition CAS have P,Q-rich sequences that promote promiscuous interactions typical of heat shock proteins. These types of motifs are able to stimulate both humoral and cellular response, stressing the role of CAS in the pathogenesis. Avoidance is the recommended treatment for allergy and replacement with milk of other ruminants is not advised, since cross-reactivity is detected among caseins of different species. Studies with animal models demonstrated that, in the gut, the great majority of the soluble whey proteins are absorbed by the absorptive epithelial cells; while CAS, which form micelles, promote its absorption through the Peyer´s patches which is important for the initial sensitization step. In conclusion CAS have several structural and molecular properties that inforce its central role in CMA.