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Whole Allergen

f81 Cheese, Cheddar type

f81 Cheese, Cheddar type Scientific Information

Type:

Whole Allergen

Display Name:

Cheese, Cheddar type

Summary

Cheese is a milk-derived food product, obtained from raw or pasteurized, whole or semi-skimmed, milk from various species, following a variety of industrial or artisanal physico-chemical and microbiological procedures. During cheese production, whey allergens alpha-lactalbumin and beta-lactoglobulin are removed, while caseins persist and undergo various degrees of proteolysis depending on the cheese manufacturing process. Food-related and occupational IgE sensitization to cheese has been reported.

For mold type cheese please read f82, mold type cheese.

Allergen

Nature

During cheese manufacture, the curdling (coagulation) step results in the separation of milk caseins (curd, approximately 80% of milk proteins) and milk whey (soluble) proteins [1]. The curds are used for the next steps of cheese making, which include proteolysis with breakdown of proteins into peptides [2]. Cheese contains a genuine microbiota, both inside and at the surface of the cheese (edible rind), with a great diversity of bacteria and yeasts reported in the literature [2, 3]. Yeast species which have been reported in hard and semi-hard cheese types include Candida spp (C. catenulate,C. parapsilosis, C. intermedia, among others), Kluyveromyces spp, Rhodotorula spp, Saccharomyces cerevisiae, Geotrichum spp, Trichosporon spp, Torulaspora spp, Yarrowia lipolytica [4, 5].

Tissue

Milk (raw or heated, processed), microbial and/or enzymatic components necessary for cheese production (such as pepsin and chymosin), preservation against microbial spoilage (e.g., lysozyme, antibiotics), or color (e.g., annatto) [2, 6-8].

Epidemiology

Risk factors

Milk allergy is a risk factor for cheese allergy due to shared allergenic components [1]. Atopy is a risk factor for occupational allergy to cheese [9].

Route of Exposure

Main

The main route of exposure to cheese is ingestion. 

Secondary

Occupational exposure in cheesemakers is an alternative route exposure.

Clinical Relevance

Depending on the route of exposure, allergy to cheese may present as food or respiratory allergy.

Milk

Proteolysis of milk allergens retained following cheese coagulation, i.e. mainly casein, results in cheese displaying lower allergenicity than milk, albeit higher than baked milk [2, 10, 11]. Aging, or ripening, of cheese results in continued proteolysis [11, 12]. Among patients with proved allergy to cow’s milk, a substantial fraction (58%) tolerated hard cheese ingestion [13].

Enzymes, preservatives, and dyes

Lysozyme-containing hard cheese induced clinical reactions in a minority of egg-allergic, lysozyme-sensitized pediatric patients, but not in adult patients [7, 14].

Food allergy to dyes used for cheese (e.g. annatto) has been reported as anaphylaxis in a 58-year old atopic patient [8].

Occupational rhinitis and asthma may be caused by ingredients added during cheese manufacture such as enzymes (e.g. calf chymosin) from natural or artificial rennet [9].

Molecular Aspects

Allergenic molecules

Caseins are the main milk allergens retained in cheese. Caseins undergoes physico-chemical and enzymatic processing resulting in lower allergenicity as compared to milk, but greater than allergenicity of heat-denatured casein from baked milk [11]. These processes take place during cheese ripening, and in a study addressing the microbiota and ripening duration of the raw milk, hard cheese Parmigiano Reggiano, it was demonstrated that the duration of ripening was the most important determinant of the peptide spectrum [12].

Caseins from cow’s milk, but not from ewe’s milk or goat milk, are included in the IUIS/WHO Nomenclature as of June 20, 2022 [15].

Name

Biochemical activity

Molecular weight (kDa)

Glycosylation

Major/minor allergen

Marker allergen

IUIS

Reference

Bos d 8

caseins (casein family)

20-30

(variable)

Major

Yes

Yes

[1, 15]

Bos d 9

alphaS1-casein

23.6

No

Major

Yes

Yes

[1, 15]

Bos d 10

alphaS2-casein

25.2

No

Major

Yes

Yes

[1, 15]

Bos d 11

beta-casein

24

No

Major

Yes

Yes

[1, 15]

Bos d 12

kappa-casein

19

Yes

Major

Yes

Yes

[1, 15]

Name

Biochemical activity

Molecular weight (kDa)

Glycosylation

Major/minor allergen

Marker allergen

IUIS

Reference

Cross-reactivity

Severe clinical reactions to ewe’s milk cheese and goat’s milk cheese may occur upon consumption by patients otherwise tolerant to cow’s milk products [16].

A variety of allergenic fungal species may grow on hard and semi-hard cheese as a result of food spoilage, including Aspergillus flavus, Aspergillus niger, and various Penicillium spp [5].

References
  1. Matricardi, P.M., et al., EAACI Molecular Allergology User's Guide. Pediatr Allergy Immunol, 2016. 27 Suppl 23: p. 1-250.
  2. Villa, C., et al., Bovine Milk Allergens: A Comprehensive Review. Compr Rev Food Sci Food Saf, 2018. 17(1): p. 137-164.
  3. Kovacs, A.T., A fungal scent from the cheese. Environ Microbiol, 2020. 22(11): p. 4524-4526.
  4. Bintsis, T., Yeasts in different types of cheese. AIMS Microbiol, 2021. 7(4): p. 447-470.
  5. Banjara, N., M.J. Suhr, and H.E. Hallen-Adams, Diversity of yeast and mold species from a variety of cheese types. Curr Microbiol, 2015. 70(6): p. 792-800.
  6. Agnolucci, M., et al., Use of chitosan and tannins as alternatives to antibiotics to control mold growth on PDO Pecorino Toscano cheese rind. Food Microbiol, 2020. 92: p. 103598.
  7. Marseglia, A., et al., Outcome of oral provocation test in egg-sensitive children receiving semi-fat hard cheese Grana Padano PDO (protected designation of origin) containing, or not, lysozyme. Eur J Nutr, 2013. 52(3): p. 877-83.
  8. Ebo, D.G., et al., Allergy for cheese: evidence for an IgE-mediated reaction from the natural dye annatto. Allergy, 2009. 64(10): p. 1558-1560.
  9. Gomez Torrijos, E., et al., Occupational allergic respiratory disease (rinoconjunctivitis and asthma) in a cheese factory worker. J Allergy Clin Immunol Pract, 2018. 6(4): p. 1416-1417.
  10. Biscola, V., et al., Brazilian artisanal ripened cheeses as sources of proteolytic lactic acid bacteria capable of reducing cow milk allergy. J Appl Microbiol, 2018. 125(2): p. 564-574.
  11. Ivens, K.O., et al., Effect of proteolysis during Cheddar cheese aging on the detection of milk protein residues by ELISA. J Dairy Sci, 2017. 100(3): p. 1629-1639.
  12. Bottari, B., et al., The Interrelationship Between Microbiota and Peptides During Ripening as a Driver for Parmigiano Reggiano Cheese Quality. Front Microbiol, 2020. 11: p. 581658.
  13. Alessandri, C., et al., Tolerability of a fully maturated cheese in cow's milk allergic children: biochemical, immunochemical, and clinical aspects. PLoS One, 2012. 7(7): p. e40945.
  14. Rossi, F., et al., Immunological response in egg-sensitive adults challenged with cheese containing or not containing lysozyme. J Am Coll Nutr, 2012. 31(6): p. 385-91.
  15. IUIS/WHO. IUIS/WHO Bos domesticus allergens.  2022 June 19]; Available from: http://allergen.org/search.php?allergenname=&allergensource=Bos+domesticus+%28Bos+taurus%29&TaxSource=&TaxOrder=&foodallerg=all&bioname=.
  16. Vinas, M., et al., Allergy to goat and sheep cheese with tolerance to cow's milk and its derivatives. Allergol Immunopathol (Madr), 2014. 42(3): p. 186-90.