Casein

Further Reading

Cow's milk f2

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Code: f78
Latin name: Bos spp.
Source material: Purified bovine casein
Casein is a major allergen in milk and the main protein constituent in cheese.

Allergen Exposure

Milk and dairy products, especially cheese. 
Food containing milk.

Casein is a heat stable major allergen in milk and the main protein constituent in cheese.
 
Unexpected exposure
Food containing undeclared milk products.
May occur in "milk-free" products as undegraded residual milk proteins or as contamination from previous productions of food containing milk.

Potential Cross-Reactivity

Milk products, especially cheese, from related animals.

Clinical Experience

IgE-mediated reactions
IgE-antibodies to casein are common in milk-sensitized patients.

Casein is a major allergen in milk (1) and the main protein constituent of cheese.

Even highly hydrolyzed milk-derived infant formulas may contain allergenic casein residues (2,3,4,5). Gern et al. (6) reported casein as a cause of allergic reactions in patients eating so-called "non-dairy" products. Casein and caseinates are used as extenders and tenderizers in imitation sausages, loaves, soups and stews. It is often used to nutritionally fortify foods and as a supplement because of the high protein content and quality, the low level of lactose and the bland flavor. Such nutritionally fortified foods include high-protein beverage powders, fortified cereals, infant formula and nutrition bars. Other uses include coffee whiteners, sauces, ice cream, salad dressing, formulated meats, bakery glazes, and whipped toppings.
 
Casein makes up about 75-80% of all milk protein and is heat stable. The concentration in cow’s milk is between 2.5-3.2% or 3.2g per 100ml milk. It was isolated from milk and has been marketed commercially since 1900. Høst (7) states that even high pasteurization (120°C for 20 minutes) only reduces but does not eliminate the allergenicity of the caseins.
 
Clinical experience
When studying 92 cow’s milk-allergic patients, Bernard et al. (8) found that there is a great variability in the specificity and intensity of IgE response to the four major casein fractions: aS1; b‚ aS2; and k indicating presence of distinct epitopes on the individual casein molecules.
 
Further studies have confirmed that a-casein largely lacks a tertiary structure and therefore also conformational epitopes (9, 10). The sequential epitopes are exposed even in denatured casein resulting in an apparent stability of the allergen to denaturing conditions, e.g. heat.
 
In a case study of a 29-year old becoming suddenly allergic to cow’s milk, the patient also had skin sensitivity to casein (11).
 
IgE antibody analysis as well as in vivo testing confirmed a monospecific reactivity to casein in a case of anaphylaxis from cow’s milk (12).

References

  1. Docena, GH; Fernandez, R; Chirdo, FG; Fossati, CA. Identification of casein as the major allergenic and antigenic protein of cow’s milk. Allergy; 1996; 51: 412-416.
  2. Oldæus, G; Björkstén, B; Einarsson, R; Kjellman, N-IM. Antigenicity and allergenicicity of cow milk hydrolysates intended for infant feeding. Pediatr Allergy Immunol; 1991; 4: 156-164.
  3. Sampson, HA; James, JM; Bernhisel-Broadbent, J. Safety of an amino-acid derived infant formula in children allergic to cow milk. Pediatrics; 1992; 90: 463-465.
  4. Chiancone, E; Gattoni, M; Giampietro, PG; Ragno, V; Businco, L. Detectoion of undegraded b -lactoglobulins and evaluation of the molecular weight of peptides in hydrolysate cow’s milk formula. J Investig Allergol Clin Immunol; 1995; 5: 228-233.
  5. Plebani, A; Restani, P; Naselli, A; Galli, CL; Meini, A; Cavagni, G; Ugazio, AG; Poiesi, C. Monoclonal and polyclonal antibodies against casein components of cow milk for evaluation of residual antigenic activity in "hypoallergenic" infant formulas. Clin Exp Allergy; 1997; 27: 949-956.
  6. Gern, JE; Yang, E; Evrard, HM; Sampson, HA. Allergic reactions to milk-contaminated "nondairy" products. New Eng J Med; 1991; 324: 976-979.
  7. Kilshaw, PJ; Effects of heat treatment of cow’s milk and whey on the nutritional quality and antigenic properties. Arch Dis Child; 1982; 57: 842- 847.
  8. Bernard, H; Wal, JM; Creminon, C; Grassi, J; Zevaco, C; Miranda, G; Houdebine, LM. Sensitivities of cow's milk allergic patients to caseins. Allergy; 1992; 47: 307.
  9. Kohno, Y; Honma, K; Saito, K; Shimojo, N; Tsunoo, H; Kaminogawa, S; Niimi, H. Preferential recognition of primary protein structures of a-casein by IgG and IgE antibodies of patients with milk allergy. Ann Allergy; 1994; 73: 419-422.
  10. Spuergin, P; Mueller, H; Walter, M; Schiltz, E; Forster, J. Allergenic epitopes of bovine a S1-casein recognized by human IgE and IgG. Allergy; 1996; 51; 306-312.
  11. Olalde, S; Bensabat, Z; Vives, R; Fernandez, L; Cabeza, N; Rodriguez, J. Allergy to cow's milk with onset in adult life. Ann Allergy; 1989; 62: 185a-185b.
  12. Tabar, AI; Alvarez, MJ; Echechipía, S; Acero, S; Garcia, BE; Olaguíbel, JM. Anaphylaxis from cow’s milk casein. Allergy; 1996; 51: 343-345.
  13. Host, A; Husby, S; Gjesing, B; Larsen, JN; Lowenstein, H; Prospective estimation of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbumin in relation to repeated milk challenge and clinical course of cow milk allergy. Allergy;1992; 47:218-229.

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.