Food Biochemistry and Food Processing (2 edition)

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42 Food Allergens 801

provide nutritional requirements of neonates. Human milk and

the milks of dairy animals, such as cows, goats, sheep and buf-

faloes, have been extensively studied. Humans are the only

known mammals that consume the milk of other mammals,

particularly from cows. In fact, cow’s milk and cow’s milk-

associated food have been deeply rooted as an important part

of the human diet, and the dairy industry plays a huge role in

supporting nutrition of humans and continues to be a backbone

of the agri-food sector in many countries.

In developed countries, bovine milk and milk-derived prod-

ucts contribute about 19% of total dietary protein intake and 73%

of calcium intake (Tome et al. 2004). However, for some people,

consumption of cow’s milk and cow’s milk-derived food has to

be avoided due to milk allergy. Recent studies have indicated

that prevalence and persistence of cow’s milk allergy (CMA) in

industrialised countries may be increasing. In North America,

incidence of CMA is estimated at 2.5% in children and about

1% in the adult population with a 75% outgrowing rate at the

age of 16 (Sicherer and Sampson 2010).

Milk Protein

Milk protein is a very complex mixture of molecules. Thanks to

advanced analytical techniques, over 200 types of proteins have

been identified in bovine milk (Ng-Kwai-Hang 2002). These

proteins can be arranged into five groups: caseins, whey proteins,

milk fat globule proteins, enzymes and minor miscellaneous

proteins. Caseins and whey proteins make up almost all of the

total milk protein composition, whereas the other 3 groups are

found in trace amounts (Table 42.1). Caseins can be separated

from the other proteins by acid precipitation at pH 4.6 to form

a coagulum. However, the ratio of casein and whey in the milk

varies among different species. In human milk, the ratio is 40:60,

in equine the ratio is 50:50 and in major dairy animals (cows,

goats, sheep and buffaloes) the ratio is 80:20.

Major Milk Allergens

β-Lactoglobulin (BLG, not found in human milk) and caseins,

α-s1-casein in particular, are regarded as the principal allergens

in cow’s milk (Kaminogawa and Totsuka 2003). A recent study

of 115 CMA Japanese children identified casein as a major milk

allergen with 107 (97.3%) children reacting positively to casein-

specific IgE, whereas 51 patients (46.6%) were positive to BLG-

specific IgE (Nakano et al. 2010). However, studies on large

populations show that a high proportion of CMA patients are

sensitised to multiple milk proteins, including proteins present

in very low quantities, such as bovine serum albumin (BSA), im-

munoglobulins and lactoferrin, suggesting that all milk proteins

could be potentially allergenic. Sensitisation to caseins, BLG,

andα-lactalbumin (ALA) appear to be closely linked. However,

sensitivity to BSA seems to be completely independent. Epitope

mapping of major milk allergens has revealed multiple aller-

genic epitopic regions within each protein (Busse et al. 2002,

Cocco et al. 2003).

Caseins

Casein (CN) forms the main fraction of milk proteins and is

subdivided into a number of families, includingα-S1-,α-S2-,

β-,κ- andγ-caseins.

Theα-S1-casein (α-S1-CN) is a single-chain phosphopro-

tein of 199 amino acid residues and represents about 40% of

total casein.α-S1-CN is characterised by a high content of

proline residues without disulfide bonds and the presence of

a small amount of secondary structure, such asα-helix orβ-

sheets. Several epitope regions ofα-S1-CN recognised by hu-

man IgE antibodies have been identified. These regions include

amino acid (aa) 19–30, aa86–103 and aa141–150 (Spuergin

et al. 1996), aa181–199 (Nakajima-Adachi et al. 1998) and nine

regions from amino acid residues 17 through 194 (Chatcha-

tee et al. 2001). Reasons for the differences in the dominant

Table 42.1.Characteristics of the Major Proteins in Human and Cow’s Milk

Proteins Human (mg/mL) Cow (mg/mL)

Molecular Weight (kDa) of

Cow’s Milk Proteins

Number of Amino

Acids in Cow’s Milk

Whole caseins

α-s1-Casein 0 11.6 23.6 199

α-s2-Casein 0 3 25.2 207

β-Casein 2.2 9.6 24 209

κ-Casein 0.4 3.6 19 169

γ-Casein 0 1.6 11.6–20.5

Whey proteins

β-Lactoglobulin 0 3 5.3 162

α-Lactalbumin 2.2 1.2 4.8 123

Immunoglobulins 0.8 0.6 < 150

Serum albumin 0.4 0.4 66.4 582

Lactoferrin 1.4 0.3 76.2 703

Other 1.3 0.6