Dairy

Casein and Whey proteins are the two major allergenic proteins found in milk.

Overview of Milk Allergy

Milk allergy is a common food allergy, particularly in infants and young children, but it can persist into adulthood. It is an immune response to milk proteins, primarily casein and whey.

Milk Sources That Can Trigger Allergic Reactions

• Cow’s Milk (Most common)
• Goat’s Milk
• Sheep’s Milk
• Buffalo Milk
• Other Mammalian Milk Sources (e.g., camel, horse)

Allergenic Proteins in Milk

Allergen Name	Protein Family	Molecular Weight (kDa)	Stability	Cross-Reactivity
Casein (Bos d 8)	Phosphoproteins	~23-25 kDa	Heat-Stable, Digestion-Resistant	Goat, Sheep, Buffalo Milk
α-Lactalbumin (Bos d 4)	Whey Protein	~14 kDa	Heat-Labile	Moderate with other animal milks
β-Lactoglobulin (Bos d 5)	Whey Protein	~18 kDa	Heat-Labile	High with other animal milks
Serum Albumin (Bos d 6)	Serum Protein	~66 kDa	Moderate Stability	Beef, Other Dairy

Key Differences Between Casein and Whey Proteins:

Casein (Bos d 8)

• Makes up 80% of the protein in milk.
• Heat-stable → Resistant to pasteurization and cooking.
• More allergenic and cross-reactive with other mammalian milks.
• Found in cheese, butter, yogurt, and processed foods.

Whey Proteins (Bos d 4, Bos d 5)

• Make up ~20% of milk proteins.
• More sensitive to heat and digestion.
• Found in protein supplements, infant formula, dairy drinks.

Cross-Reactivity with Other Foods

Milk Allergy Cross-Reactivity

• Goat, Sheep, Buffalo Milk: High cross-reactivity (casein proteins are highly conserved).
• Beef and Bovine Products: Possible reaction due to Bos d 6 (Serum Albumin).
• Soy Protein: Some individuals develop cross-reactivity between milk and soy proteins.
• Eggs, Peanuts, Wheat: Co-allergies are common but not due to direct cross-reactivity.

Clinical Implications:

• Casein Allergy → Avoid all dairy, including processed foods.
• Whey Allergy → May tolerate some dairy if extensively heated.
• Severe Reactions → Strict avoidance of even trace amounts in foods.

Epitope Mapping of Casein and Whey Allergens

Casein (Bos d 8)

• Regions with IgE-binding epitopes:
  • Amino acids: 30–50, 100–120, 180–200
  • Core IgE-binding sites: Hydrophobic regions
• Clinical Significance:
  • Highly stable allergen, causing severe reactions.
  • Can trigger delayed allergic responses.

β-Lactoglobulin (Bos d 5)

• Regions with IgE-binding epitopes:
  • Amino acids: 40–60, 150–170
  • Core IgE-binding sites: Beta-sheet structures
• Clinical Significance:
  • More heat-sensitive than casein.
  • Linked to immediate-type milk allergy symptoms.

Symptoms of Milk Allergy

Milk allergy can cause IgE-mediated reactions (immediate) or non-IgE reactions (delayed).

Immediate Reactions (IgE-Mediated)

• Hives, swelling, redness (urticaria, angioedema)
• Vomiting, diarrhea, abdominal pain
• Wheezing, coughing, difficulty breathing
• Anaphylaxis (severe cases, requires epinephrine)

Delayed Reactions (Non-IgE Mediated)

• Eosinophilic esophagitis (EoE)
• Food protein-induced enterocolitis syndrome (FPIES)
• Chronic diarrhea, reflux, colic in infants

Diagnosis of Milk Allergy

Skin Prick Test (SPT)

• Detects IgE response to milk proteins.

Serum IgE Testing

• Measures IgE antibodies to casein and whey proteins.

Oral Food Challenge (OFC)

• Gold standard for confirming milk allergy.
• Performed under medical supervision.

Atopy Patch Testing

Used for delayed (non-IgE) reactions.

Management and Treatment

Strict Milk Avoidance

• Avoid all dairy products, including hidden sources.
• Read labels carefully for casein, whey, lactose-containing ingredients.

Alternative Milk Options

Milk Substitute	Suitable for Milk Allergy?
Soy Milk	Yes (unless allergic to soy)
Almond Milk	Yes (unless allergic to tree nuts)
Oat Milk	Yes
Rice Milk	Yes
Coconut Milk	Yes (unless cross-reactive)
Goat/Sheep Milk	No (cross-reactivity)

Emergency Treatment for Severe Reactions

• Epinephrine (EpiPen®) for anaphylaxis.
• Antihistamines for mild reactions.
• Corticosteroids for prolonged reactions.

Oral Immunotherapy (OIT)

• Experimental for milk allergy desensitization.
• Not recommended for anaphylactic patients.

Comparison with Other Food Allergies

Allergy Type	Major Allergens	Cross-Reactive Foods	Heat Stability	Risk of Anaphylaxis
Milk Allergy	Casein, Whey	Goat/Sheep Milk, Beef	High (Casein), Low (Whey)	High
Peanut Allergy	Ara h Proteins	Tree Nuts, Soy	High	Very High
Tree Nut Allergy	Jug r, Pis v Proteins	Other Nuts, Peanuts	High	Very High
Egg Allergy	Ovomucoid, Ovalbumin	Chicken, Duck Eggs	Low	Moderate
Soy Allergy	Gly m Proteins	Peanuts, Legumes	Moderate	Low-Moderate

Summary of Milk Allergy

• Milk allergy is caused by casein and whey proteins.
• Casein is more heat-resistant and cross-reactive with goat/sheep milk.
• Symptoms range from mild to severe anaphylaxis.
• Strict dairy avoidance and alternative milk options are essential.
• Diagnosis involves skin tests, serum IgE, and food challenges.

FDA-Recognized Major Milk Protein Allergens with Common and Scientific Names

Common/Usual Name	Scientific Name
Casein	Bos d 8 (Total Casein)
Alpha-Casein	Bos d 9 (Alpha-Casein)
Beta-Casein	Bos d 10 (Beta-Casein)
Kappa-Casein	Bos d 11 (Kappa-Casein)
Whey Protein	Bos d Whey
Alpha-Lactalbumin	Bos d 4 (Alpha-Lactalbumin)
Beta-Lactoglobulin	Bos d 5 (Beta-Lactoglobulin)
Immunoglobulins	Bos d Ig
Bovine Serum Albumin (BSA)	Bos d 6 (Bovine Serum Albumin, BSA)
Lactoferrin	Bos d LF (Lactoferrin)

Key Insights:

• Casein proteins (Bos d 8, Bos d 9, Bos d 10, Bos d 11) are the primary milk allergens, making up about 80% of milk proteins and are highly heat-stable.
• Whey proteins (Bos d 4 – Alpha-Lactalbumin, Bos d 5 – Beta-Lactoglobulin) are the second major allergen group, making up about 20% of milk proteins, and are more heat-labile.
• Bovine Serum Albumin (Bos d 6) and Immunoglobulins (Bos d Ig) can also trigger reactions, particularly in individuals with beef allergies due to cross-reactivity.
• Lactoferrin (Bos d LF) is a minor milk allergen, but it may contribute to immune reactions in sensitive individuals.