Allergen

Cow's milk (CM) is popularly consumed throughout the world. Allergy to CM is prevalent among infants and young children during the first year of life, affecting 0.5-3% at the age of 1 year. Bos d 6 (bovine serum albumin) has been reported as a minor allergenic whey protein in CM. According to a number of studies, sensitization towards Bos d 6 ranges between 43-92.9% of patients with CM allergy (CMA). Bos d 6 is the most heat-labile protein among the other whey proteins and therefore is likely to be destroyed after boiling CM. Thus, specific immunoglobulin E to Bos d 6 might help evaluate tolerance to boiled milk. Clinical manifestations of Bos d 6-mediated allergy majorly include anaphylaxis. Moreover, sensitization to Bos d 6 is regarded as a predictive marker of CMA in children with beef allergies. Cross-reactivity has been observed between serum albumin of cow, deer, dog, sheep, pork, and cat

Epidemiology

Worldwide distribution

Cow’s milk (CM) is a popular food consumed worldwide. However, CM allergy (CMA) is prevalent among infants and young children, with a high prevalence observed during the first year of life, affecting 0.5-3% at the age of 1 year.

Bos d 6 is bovine serum albumin (BSA) and a minor allergenic whey protein in CM. According to a study, 43% of patients with CMA (n=92) are found to be sensitized to Bos d 6. According to another clinical study, 61.3% of children allergic to CM (n=80) reported sensitization towards Bos d 6 (based on immunoblotting).

In an Italian in-vitro study, 45% (9/20) of pediatric patients allergic to CM exhibited sensitization to Bos d 6. As per another study conducted in Italy, sensitization to Bos d 6 was observed in 92.9% (26/28) of the children allergic to CM.

Furthermore, specific immunoglobulin E (sIgE) against Bos d 6 was reported among 45.5% of patients with CMA (n=86) in an Iran-based study. And in a study conducted in Denmark among 39 milk-allergic infants [21 infants with IgE-CMA (CMA) and 18 infants with non-IgE CMA (CMI)], the frequency of sIgEs to Bos d 6 was highest before (12/17 for CMA; 9/13 for CMI) and after (15/20 for CMA; 15/17 for CMI) the milk challenge at 12 months in comparison to other cow milk proteins.

Moreover, a study conducted in Europe reported the presence of sIgE towards Bos d 6 in 3.8% of the patients (children and adults) with CMA (n=73). A study used crossed radioimmunoelectrophoresis technique to determine the serum IgE level to CM antigenic components in the sera of 21 CMA patients and detected IgE antibodies against bovine albumin in the sera of all patients.

Clinical Relevance

Disease severity

CMA is considered as a major common pediatric food allergy. Milk allergy can be either IgE-mediated or non-IgE-mediated. The clinical manifestations of CM protein allergy are reported to be of two types such as immediate (shortly after consumption) and delayed (after hours or days of consumption) responses. The immediate reactions are generally IgE-mediated and can lead to angioedema, urticaria, aggravation of atopic dermatitis (AD), vomiting, in some cases, anaphylaxis, as well as respiratory symptoms (breathing, wheezing, coughing). On the other hand, most delayed reactions are non-IgE mediated and can lead to gastrointestinal symptoms (like enteropathy or proctocolitis) or skin reactions (such as AD).

As per a study conducted in Iran, anaphylactic reactions were observed in 60% of the patients with CMA showing a positive test for sIgE towards Bos d 6.

Cross-reactive molecules

BSA is a minor allergen in milk (Bos d 6) but a major allergen in beef. Thus, patients with milk allergy sensitized to Bos d 6 may have a concomitant beef allergy, and BSA has also been found to cross-react with other BSA such as pork and sheep.

A prospective cohort study conducted on 38 children (age <14 years) with CMA-associated symptoms detected the rate of cross-sensitization (SPT-based) between goat milk and cow milk to be 63.2% (24/38).

According to a study, the cross-reactivity found between SA of cow, pork, deer, sheep, dog, and, cat (meat and/or epithelia) in the sera of all the patients with persistent milk allergy (n=8) was inhibited by pure Bos d 6.

An Egypt-based study reported cross-reactivity between CM and beef in 30 patients with CMA.

Diagnostics

Disease Severity

In an Italy-based study, 92.9% of children with beef allergy were also allergic to CM. Thus, sensitization to Bos d 6 was a predictive marker of CMA in children with beef allergy.

Exposure

Cow milk allergy mainly occurs through ingestion.

Explained Results

Allergen information

Bos d 6 (bovine serum albumin) is a minor allergenic protein found in CM and is the most heat-labile protein of all the milk proteins.

Clinical relevance

Typical symptoms of CMA include skin reactions (angioedema, urticaria, and atopic dermatitis), GI symptoms, respiratory systems, and in some cases, anaphylaxis.

Cross-reactivity

Bos d 6 (BSA) from CM has been found to show cross-reactivity with SA of deer, pork, sheep, dog, and cat (meat and/or epithelia). Moreover, cross-reactivity has also been reported between CM and beef.