Type:
Whole Allergen
Whole Allergen
Whole Allergen
Cheese, Cheddar type
f81
XM5GA5
(ICD-11 is currently under implementation by WHO and the ICD-11 codes displayed in the encyclopedia may not yet be available in all countries)
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.
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].
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].
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].
The main route of exposure to cheese is ingestion.
Occupational exposure in cheesemakers is an alternative route exposure.
Depending on the route of exposure, allergy to cheese may present as food or respiratory allergy.
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].
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].
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] |
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].