Allergen Data Collection: Beef (Bos domesticus)
Internet Symposium on Food Allergens 3(4):171-84 (2001) [http://www.food-allergens.de]
1 Prevalence of Beef Allergy

Prevalence data are based on different diagnostic procedures. While the prevalence of sensitization (sensitivity) can be estimated by SPT, RAST, and immunoblot, a clinical relevant sensitization (allergy) is evaluated by convincing history (anamnesis) or food challenge tests (ideally by DBPCFC).

1.1 Subjects with Atopic or Other Diseases
 
Country / Subjects Sensitivity / Allergy to References
Australia, Melbourne
96 cow's milk allergic children
beef 15% (adverse reactions reported by parents) Bishop et al. 1990
Hill et al. 1997
France
34 idiopathic nephrotic syndrome (INS) patients with or without atopic manifestations
beef 18% (human basophil degranulation test) Lagrue et al. 1986
France
80 cases of food- related anaphylaxis (from 1993-97)
beef 1.3% (reported to CICBAA databank) European Commission 1998
France, Pierre Benite
60 cases of anaphylaxis (study period 1984-92)
beef 1.7% Andre et al. 1994
France, Nancy and Toulouse
544 food allergic children
beef 1.5% (food challenge) Rance et al. 1999b
Italy, Milano
184 children with atopic dermatitis and positive SPT to foods
raw beef 11% (SPT)
raw beef 6.5% (anamnesis, DBPCFC)
Fiocchi et al. 1995a
Italy, Parma
31 children with atopic dermatitis
beef 3.2% (RAST) Caffarelli et al. 2001
Malaysia, Kuala Lumpur
148 adults with symptoms of nasal congestion and rhinorrhea
beef 12% (SPT) Gendeh et al. 2000
South Africa, Cape Town
112 children with atopic dermatitis
beef 3.1% (reported by parents) Steinman & Potter 1994
Switzerland, Zurich
402 food allergic adults (study period 1978-87)
beef and pork 4.5% Wüthrich 1993
Switzerland, Zurich
383 food allergic patients (study period 1990-94)
beef 2.9% Etesamifar & Wüthrich 1998
UK, London
100 patients with food intolerance
beef 2% (n = 51, SPT)
beef 2% (repeated challenge)
Lessof et al. 1980
USA, Baltimore, MD
335 children referred for evaluation of atopic dermatitis and possible food allergy
beef 27% (SPT)
beef 3.3% (DBPCFC)
Werfel et al. 1997
USA, Baltimore, MD
25 cow's milk allergic subjects (DBPCFC)
beef 84% (SPT)
beef 20% (DBPCFC)
Werfel et al. 1997
USA, Durham, NC
113 atopic children
beef 16% (SPT)
beef 1.8% (DBPCFC)
Sampson & McCaskill 1985
USA, Little Rock, AR
165 patients with atopic dermatitis
beef 7.9% (SPT) from which 8% were DBPCFC-positive (n=12) Burks et al. 1998
USA, Memphis, TN
266 patients with anaphylaxis (age of 12-75 years, study period 1978-92)
beef 6.7% (from 89 food-induced cases of anaphylaxis) Kemp et al. 1995

1.2 Prevalence of Associated Allergies
 
Country / Subjects Sensitivity / Allergy to References
Italy, Milano
27 beef-allergic children (DBPCFC) (age of 0.75-4.66 years, study period 1992-99)
cow's milk 93% (SPT)
cow's milk 93% (DBPCFC)
Fiocchi et al. 2001a
USA, Baltimore, MD
11 beef-allergic patients (DBPCFC)
cow's milk 73% (DBPCFC) Werfel et al. 1997
USA, New Orleans, LA
57 subjects with suspected meat allergy
beef 73%
lamb 71%
pork 58%
venison 59%
chicken 41%
turkey 38%
(grid immunoblot)
Ayuso et al. 1999

2 Outgrowing of Beef Allergy
 
Country / Subjects Sensitivity / Allergy References
Italy, Milano
27 beef-allergic children (DBPCFC) (median age of 2.54 years, range  0.75-4.66 years, study period 1992-99)
Loss of beef allergy in 89% within median of 3 years, range 0.83-4.83 years (tolerance to beef prospectively evaluated by DBPCFC on yearly basis) Fiocchi et al. 2001b
USA, Baltimore, MD
11 beef-allergic children (age of 16 months to 14 years) (DBPCFC)
Loss of beef allergy in 36% within 2 years after diagnosis (DBPCFC) Werfel et al. 1997

3 Symptoms of Beef Allergy
 
Symptoms & Case Reports References
systemic reactions
anaphylaxis (14), excercise induced anaphylaxis (15) 

cutaneous symptoms
angioedema (6), contact dermatitis (4, 11, 13), hand dermatitis (1), itching of ears, face, and hands (9), edema (10), lip edema (12), pruritic lips (10), nasal pruritus (10), pruritic and erythamtous rash (10), urticaria (6, 10), contact urticaria (3), generalized urticaria (8, 10, 15) 

gastrointestinal symptoms
abdominal pain (9), diarrhea (9), eosinophilic gastroenteritis (7), nausea (9), oral pruritus (10), vomiting (10)

respiratory symptoms
asthma (8, 10, 12), cough (8, 12), dyspnea (10), allergic rhinitis (8, 12)

other symptoms
migraine (2, 5), ocular and nasal symptoms (rhinorrhea) (10)

(1) Fisher & Stengel 1977
(2) Grant 1979
(3) Fisher 1982
(4) Jovanovic et al. 1992
(5) Mylek et al. 1992
(6) de Blay et al. 1993
(7) Verdaguer et al. 1993
(8) Fiocchi et al. 1995a
(9) Wüthrich 1996
(10) Werfel et al. 1997
(11) Boehncke et al. 1998
(12) Fiocchi et al. 1998b
(13) Iliev & Wüthrich 1998
(14) Kanny et al. 1998
(15) Biedermann et al. 1999
Percentage of Reactions
Asthma in 7.7%, allergic rhinitis and asthma in 23%, lip edema and coughing in 7.7%, urticaria in 46%, and allergic rhinitis and urticaria in 15% of patients (13 beef allergic children, DBPCFC) (1)
(1) Fiocchi et al. 1998b
Threshold for Elicitation of Symptoms
Doses between 10 and 16 g of well-cooked beef elicited allergic symptoms in 36% of patients, doses between 30 and 60 g in 55%, and a dose of 250 g in 9% (DBPCFC, 11 beef allergic patients aged between 16 months and 14 years) (2)
The total dose of 90 mg bovine serum albumin (corresponding to the amount present in 180 g of calf meat) elicited immediate reactions in 3 children  (12 beef allergic children, DBPCFC) (1)
Positive reaction to 55 mg of bovine serum albumin (1 beef allergic adult, DBPCFC) (3)
(1) Fiocchi et al. 1995a
(2) Werfel et al. 1997
(3) Kanny et al. 1998

4 Diagnostic Features of Beef Allergy
 
Parameters / Subjects Outcome References
SPT, Clinical Relevance
4 reportedly beef allergic subjects
25% had positive SPT Boccafogli et al. 1994
SPT, Clinical Relevance
20 beef allergic children (DBPCFC) (median age of 2.29 years, range 1-4.33 years, study period 1992-96)
SPT commercial fresh food
sensitivity 90% 100%
specificity 85% 85%
Fiocchi et al. 1998a
IgE, Clinical Relevance
34 children with atopic dermatitis (20 DBPCFC positive, 14 DBPCFC negative to beef) (median age of 2.26 years, range 1-4.41 years)
sensitivity 90%
specificity 57%
cut-off point 1.8 kU/L
(RAST)
Fiocchi et al. 2000
IgE, Clinical Relevance
41 beef sensitive subjects
29% had a clinically relevant beef allergy (SDS-PAGE immunoblot) Ayuso et al. 1999

5 Therapy of Beef Allergy
 
Treatment* Outcome References
Elimination Diet
Infants with beef and cow's milk allergy
High therapeutic effect of canned pork meat and horse meat formulas in the diet of infants Ladodo et al. 1989
Oral Desensitization
After elimination diet for 1 year oral desensitization was performed with extracts from raw beef, veal, and pork in dilutions from 1:10 million and 1:1000 over a period of 3 years (a beef and pork allergic woman)
After the treatment the patient could eat 100 g beef or pork up to 4 times a week; suddenly a relapse with severe allergic symptoms occurred after ingestion of beef; then a strict elimination diet was followed again Wüthrich 1996
* Studies may be experimental, unproved, or controversial. Please notice the disclaimer !

6 Composition of Beef

7 Allergens of Beef
 
Proteins / Glycoproteins Allergen Nomenclature* References
Bovine Serum Albumin [67 kDa] Bos d 6 Restani et al. 1997a, Werfel et al. 1997, Han et al. 2000
Immunoglobulin [160 kDa] Bos d 7 Werfel et al. 1997, Ayuso et al. 2000, Han et al. 2000
Actin, Myoglobin   Restani et al. 1997a
Allergens: 160, 66, 45, 38, and 21 kDa   Ayuso et al. 2000
* current list of the Allergen Nomenclature Sub-Committee 2001

7.1 Sensitization to Beef Allergens
 
Country / Subjects Sensitivity to References
Italy, Milan
10 children with positive SPT to raw and cooked beef and positive DBPCFC to cooked beef
bovine serum albumin 100% (SPT) Fiocchi et al. 1998b
USA, New Orleans, LA
a) 12 beef allergic subjects
b) 29 beef tolerant subjects
(5 months to 48 years of age)
Allergens in raw beef: a) b)
160 kDa (bovine IgG) 83% 24%
66 kDa 25% 27%
45 kDa 17% 20%
(SDS-PAGE immunoblot)
Ayuso et al. 2000

7.2 Bovine Serum Albumin

8 Isolation & Preparation
 
Extract / Purified Allergens Methods References
Protein extract Ground raw beef was pulverized and extracted with PBS buffer (pH 7.4) overnight at 4°C, then centrifuged, the fat removed and centrifuged again Werfel et al. 1997
Bovine serum albumin Isolation by cold alcohol precipitation Fiocchi et al. 1995a
bovine IgG Acid precipitation of colostral whey and concentration of supernatant, isolation of IgG by affinity chromatography (Avid Gel AL) and further purification by IEC, dialysis, lyophylization Lefranc-Millot et al. 1996

 
9 Cross-Reactivities
 
Cross-Reacting Allergens Subjects / Methods References
Beef: (Lamb)
serum albumins from beef and lamb*
Significant correlations in SPT between bovine and ovine serum albumins (r = 0.846, p < 0.0001) and between beef and lamb meat (R = 0.771, p < 0.005) (All 12 children SPT positive to bovine and ovine meat, and to serum albumins);
6 of 12 children were RAST positive to bovine meat, 3 to lamb meat, 4 to bovine serum albumin and 3 to ovine serum albumin;
in DBPCFC 3 children were positive to bovine serum albumin and 4 to ovine serum albumin (another child had a delayed reaction to ovine serum albumin)
Fiocchi et al. 1995a
Beef: (Lamb, Venison, Milk)
bovine IgG, lamb, venison, and milk
Inhibition of IgE to bovine IgG by lamb and venison extracts and milk Ayuso et al. 2000
Beef: (Pork, Sheep)
serum albumins from beef, pork, and sheep
Cross-reactivity between purified bovine, pig, and ovine serum albumins was demonstrated; no cross-reactivity with serum albumins from horse, rabbit, turkey, and chicken  (SDS-PAGE immunoblot inhibition, beef allergic patients with bovine serum albumin specific serum IgE) Restani et al. 1997a, 1998
Beef: (Cow's Milk)
beef, cow's milk*
8/11 beef allergic children presented concomitant reactivity to cow's milk (DBPCFC)* Werfel et al. 1997
Bovine Gelatin: (Fish Gelatin)
bovine and fish gelatin
Little cross-reactivity between fish and bovine gelatins (pooled serum from fish gelatin sensitive patients) Sakaguchi et al. 2000
*  multiple sensitization (not proved by inhibition-tests)
 
 
Unique Allergens Subjects / Methods References
Beef (Pork, Chicken)
Beef  vs pork and chicken
No IgE- binding from sera of 10 beef allergic individuals to pork and chicken meat extracts  (ELISA, SDS-PAGE immunoblot) Han et al. 2000

10 Stability of Beef Allergens
 
Treatment Effects References
Homogenization, Lyophilization
homogenized beef and freeze-dried beef
2 children with weak reactions in SPT (12 children with beef allergy) Fiocchi et al. 1995b
Homogenization, Lyophilization
1) homogenized beef
2) freeze-dried beef
1) no positive reactions in SPT and DBPCFC
2) 1 child positive in SPT, no positive reaction in DBPCFC (10 children with positive SPT to raw and cooked beef and positive DBPCFC to cooked beef)
Fiocchi et al. 1998b
Heat
cooked beef (100°C, 5 min)
10 toddlers with positive SPT to raw and cooked beef: Positive DBPCFC with 180 g of cooked beef Fiocchi et al. 1998b
Heat
cooked beef 
Positive SPT to raw beef and negative SPT to cooked beef in a meat allergic patient Kanny et al. 1998
Heat
cooked beef 
Stronger IgE reactivity to raw meats in comparison to cooked meats (57 sera from suspected meat-allergic subjects, grid immunoblot) Ayuso et al. 1999
Heat
cooked beef (20 min, 140°C in conventional oven)
61% of sera showed IgE-binding to proteins of raw beef only, 24% to proteins of raw and cooked beef, and 7% to cooked beef only 
(41 beef sensitive patients, SDS-PAGE immunoblot)
Ayuso et al. 2000
Heat
heated bovine serum albumin
7 children were sensitive to heated bovine serum albumin in SPT and 4 children were DBPCFC positive to bovine serum albumin (11 children with beef allergy and positive SPT to bovine serum albumin) Fiocchi et al. 1998b
Heat
cooked bovine serum albumin (100°C, 10 min)
Negative reaction to cooked bovine serum albumin (1.8 g) and positive reaction to uncooked bovine serum albumin  (55 mg) in DBPCFC in a 19-year old woman Kanny et al. 1998
Heat
a) rare-cooked beef (red centrally and pink peripherally)
b) well-cooked beef (brown)
11 beef allergic children
a) 3 children: positive DBPCFC
b) 8 children: positive DBPCFC
Werfel et al. 1997
Heat
raw and cooked beef
Allergenic potencies comparing maximal inhibition of IgE binding to raw beef: raw beef > cooked beef
(2 sera from beef allergic children, EAST inhibition)
Werfel et al. 1997
Heat
minced beef extract heated 
a) up to 2h at 85°C
b) for 20 min up to 80°C
Bovine serum albumin and gamma globulin were heat-labile, 6 protein fractions persisted heat treatment: Strongest IgE-binding to 17.8 kDa and strong IgE-binding to 19 kDa protein; weak IgE-binding to 14, 20, 45, and >60 kDa proteins (11 beef allergic children, SDS-PAGE immunoblot) Werfel et al. 1997
Heat
minced beef, purified bovine serum albumin and gamma-globulin
Heating of minced beef at 80°C:
a) bovine serum albumin stable for 10 min
b) gamma-globulin stable for 3 min
Heating of purified proteins:
a) bovine serum albumin stable for 15 min at 95°C
b) gamma-globulin stable for 15 min at 65°C
(11 beef allergic children, SDS-PAGE immunoblot)
Werfel et al. 1997
Reduction, Detergents
bovine serum albumin
1) reduction with 2-mercaptoethanol
2) SDS-treatment (and heating)
1) reduction but not elimination of IgE-binding
2) no decrease in IgE-binding of bovine serum albumin (PAGE immunoblot)
Restani et al. 1998
Reduction
reducing conditions (mercaptoethanol, iodoacetamide)
IgE reactivity to bovine IgG completely disappeared when beef extracts were separated under reducing conditions, indicating conformational epitopes (SDS-PAGE immunoblot) Ayuso et al. 2000
Pepsin Hydrolysis (Serum albumins)
hydrolysis of bovine serum albumin with pepsin a) for 5 min and b) for 2 and 4 hours
a) positive SPT in 4 children, RAST all negative
b) positive SPT in 2 children, RAST all negative
(12 children with beef allergy and positive SPT to bovine serum albumin)
Fiocchi et al. 1995b
Hydrolysis
multienzymatic in vitro digestion of meat samples (raw, steam-cooked (home-made and industrial cooking), homogenized (strained) and freeze-dried)
Enzymatic digestibility is strongly affected by heat treatment; cooking and technological treatments reduce positive responses in SPT
(8 children with , SPT and SDS-PAGE immunoblot)
Restani et al. 1997b
Pepsin Hydrolysis, Pancreatic Enzymes, Whey Proteins
hydrolysis with pepsin (pH 2, 3, and 4, for 90 min) followed by hydrolysis with a mixture of pancreatic enzymes (pH 7.5 for 150 min) of  bovine serum albumin and bovine IgG
Percent inhibition of IgE-binding from sera of patients with IgE- mediated cow's milk allergy to native proteins by respective hydrolysates of homologue protein:
pepsin hydrolysis at pH 2 pH 3 pH 4
BSA 0% 0% 58%
bovine IgG 2.5% 54% 91%
(RAST inhibition)
Schmidt et al. 1995

11 Allergen Sources

11.1 Beef Allergen Sources
 
 
Reported Adverse Reactions References
Beef see 2 Symptoms of Beef Allergy
Salami
A case of anaphylaxis induced by ingestion of a salami (source of meat not specified) (1)
 (1) Pastorello et al. 2001
Gelatine
Two cases of anaphylaxis induced by ingestion of gelatine (source not specified) (1)
(1) Pumphrey & Stanworth 1996
Pharmaceuticals
A case of IgE-mediated reactions to bovine serum albumin contained in the dilution fluid added to semen for artificial insemination (1)
(1) de Blay et al. 1993
Pharmaceuticals
Immunizing with sera containing adjuvants the subjects became sensitized to other substances in the immunizing sera, specifically to beef protein (1)

(1) Hollander 1995
Pharmaceuticals: Aprotinin
Anaphylactic reactions associated to the administration of aprotinin, either by injection route or as a biological sealant application; documented risk factors include allergy to beef meat, egg white, cheese and milk; aprotinin is a proteinase inhibitor (1)
(1) Laxenaire et al. 2000

11.2 Beef Associated Allergen Sources

The table lists adverse events due to unexpected allergens (other than beef allergens) present in a variety of beef products.
 
Reported Adverse Reactions References
Several Food Products
9 Adverse reactions to unexpected cow's milk allergens in
a) Meatballs containing 1.1% CAS (undeclared)
b) Hot dog containing 0.04% CAS (contaminated)
c) Recombined ham containing 2.6% (undeclared)
d) Sausage containing 1.0% CAS (undeclared)
e) Sausage containing 0.06% CAS (contaminated)
(1) Malmheden Yman et al. 1994
Sausage (Texturing Agent)
Severe reactions after ingestion of sausage containing CAS (texturing agent) (1)
(1) Foucard et al. 1997
Meat (Tenderizing Agent)
Asthma after long-term contact with papain dust in a supervisor of a meat tenderizer factory (1)
(1) Novey et al. 1979
Hamburger Meat (Spice)
Allergic reactions in a 40-year old meat industry worker handling flavourings for minced beef in the preparation of hamburgers; evaluation revealed IgE-mediated reactions to ginger as a ingredient of the flavourings (1)
(1) Cueva et al. 2001
"Salami Worker's Lung"
Hypersensitivity pneumonitis in a woman (56 years) due to inhaled antigens from dust in a factory producing salamis; in the cultures of the material that covered the salamis Penicillium spp. was present and the suspected cause of hypersensitivity reactions  (1)
(1) Rivero et al. 1999
Veterinary Drug Residues
Occurence of allergic reactions was demonstrated in 2/9 patients challenged with penicillin- contaminated meat (1)
Anaphylaxis on 4 occasions in a child, likely caused by beef containing streptomycin (2)
A 64 year old woman experienced anaphylactic shocks after ingestion of beef and pork meat, respectively. Food allergy to animal proteins excluded. The woman was highly sensitzed to penicillin. It was concluded that food induced anaphylaxis was linked to penicillin residues in meats (3)
(1) Lindemayr et al. 1981
(1) Tinkelman & Bock 1984
(2) Kanny et al. 1994

12 References       [Recent Reviews]

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