Milk Proteins and Immunity – Function and Allergy

What Are Milk Proteins?

Milk contains a wide variety of proteins that are nutritionally and immunologically significant for the human body. The main milk proteins are caseins (approximately 80% of the total protein in cow's milk) and whey proteins such as lactalbumin and lactoglobulin (approximately 20%). Human breast milk also contains specific immune-active proteins such as immunoglobulin A (IgA), lactoferrin, and lysozyme, which play a special role in supporting the infant immune system.

Milk Proteins and the Immune System

Milk proteins can interact with the human immune system in different ways. A fundamental distinction is made between immunostimulatory and immunomodulatory effects on one hand, and immunoreactive (allergic or inflammatory) responses on the other.

Immune-Protective Functions

Certain proteins found in breast milk have direct protective functions for the immune system of newborns:

• Lactoferrin: An iron-binding glycoprotein with antimicrobial, antiviral, and anti-inflammatory properties. It inhibits the growth of pathogenic bacteria by depriving them of iron and modulates the activity of immune cells.
• Secretory IgA (sIgA): The most abundant immunoglobulin in breast milk. It protects the mucosal surfaces of the infant from pathogens by preventing their attachment to epithelial cells.
• Lysozyme: An enzyme with antibacterial activity that destroys the cell walls of certain bacteria.
• Beta-lactoglobulin and alpha-lactalbumin: These whey proteins possess immunomodulatory properties and may support the maturation of the infant immune system.

Immunomodulation by Milk-Derived Peptides

During the digestion of milk proteins, bioactive peptides are released – short amino acid chains that can exert physiological effects. Some of these peptides, such as so-called casomorphins or beta-casein peptides, have shown immunomodulatory properties in studies. They may influence the activity of T lymphocytes and natural killer cells, and can modulate inflammatory processes.

Milk Protein Allergy and Immune Response

In some individuals – particularly infants and young children – milk proteins trigger an immune response known as cow's milk protein allergy (CMPA). This is the most common food allergy in infancy, affecting approximately 2–5% of children.

Mechanism of Milk Protein Allergy

In the classic IgE-mediated allergy, the immune system mistakenly identifies certain milk proteins – frequently casein or beta-lactoglobulin – as dangerous. It then produces specific immunoglobulin E (IgE) antibodies. Upon re-exposure to the allergen, histamine and other inflammatory mediators are released, triggering typical allergic symptoms. There are also non-IgE-mediated and mixed reactions, in which cell-mediated immune mechanisms play a role.

Symptoms of Milk Protein Allergy

• Skin reactions: hives (urticaria), eczema, skin redness
• Gastrointestinal symptoms: abdominal pain, vomiting, diarrhea, blood in stool
• Respiratory symptoms: runny nose, cough, asthma
• In rare cases: anaphylactic shock (a life-threatening reaction)

Diagnosis

The diagnosis of cow's milk protein allergy is made through a combination of medical history, skin prick testing, measurement of specific IgE antibodies in the blood, and a controlled oral food challenge (elimination diet followed by supervised reintroduction of the allergen).

Treatment and Management

The primary treatment consists of the strict avoidance of cow's milk proteins. For infants who cannot be breastfed, extensively hydrolyzed formulas or amino acid-based formulas are used. Many children develop tolerance to cow's milk proteins by school age. Oral immunotherapy (OIT) is under clinical investigation and shows promising results for desensitization.

Milk Proteins and Tolerance Development

Under normal circumstances, the immune system develops oral tolerance to dietary proteins, including milk proteins. This process is mediated by regulatory T cells (Treg cells) and begins in early childhood. Factors such as breastfeeding, gut flora (microbiome), and timing of exposure significantly influence tolerance development. Early exposure to milk proteins may, under certain conditions, reduce the risk of developing an allergy later in life.

References

1. Koletzko S. et al. - Diagnosis and Management of Cow's Milk Protein Allergy in Infants. Monatsschrift Kinderheilkunde, 2020. Springer Medizin.
2. Schuster J. et al. - Bioactive Peptides from Milk Proteins: Overview and New Findings. International Journal of Molecular Sciences, 2021. MDPI.
3. World Allergy Organization (WAO) - Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. WAO Journal, 2010 (updated 2020). Available at: www.worldallergy.org