Patients suffering from non-IgE-mediated cow's milk protein intolerance cannot be diagnosed based on IgG subclass or IgA responses to milk allergens

Allergy. 2011 Sep;66(9):1201-7. doi: 10.1111/j.1398-9995.2011.02635.x. Epub 2011 May 17.


Background: Cow's milk is one of the most common causes of food allergy. In two-thirds of patients, adverse symptoms following milk ingestion are caused by IgE-mediated allergic reactions, whereas for one-third, the mechanisms are unknown. Aim of this study was to investigate whether patients suffering from non-IgE-mediated cow's milk protein intolerance can be distinguished from persons without cow's milk protein intolerance based on serological measurement of IgG and IgA specific for purified cow's milk antigens.

Methods: We determined IgG(1-4) subclass and IgA antibody levels to purified recombinant αS1-casein, αS2-casein, β-casein, κ-casein, α-lactalbumin, and β-lactoglobulin in four patient groups by ELISA: Patients with IgE-mediated cow's milk allergy (CMA, n=25), patients with non-IgE-mediated cow's milk protein intolerance (CMPI, n=19), patients with gastrointestinal symptoms not associated with cow's milk ingestion (GI, n=15) and control persons without gastrointestinal problems (C, n=26). Cow's milk-specific IgE levels were determined by ImmunoCAP.

Results: Only CMA patients had IgE antibodies to cow's milk. Cow's milk allergic patients mounted the highest IgG(1) and IgG(4) antibody levels to αS1-casein, αS2-casein, β-casein, κ-casein, and α-lactalbumin. No elevated levels of IgG(4) , IgA, and complement-binding IgG subclasses (IgG(1) , IgG(2) , IgG(3) ) to purified cow's milk allergens were found within the CMPI patients compared to persons without cow's milk protein intolerance (GI and C groups).

Conclusion: Cow's milk protein intolerant patients cannot be distinguished from persons without cow's milk protein intolerance on the basis of IgG subclass or IgA reactivity to cow's milk allergens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allergens / immunology*
  • Animals
  • Child
  • Child, Preschool
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Epitopes / immunology
  • Female
  • Humans
  • Immunoglobulin A / blood*
  • Immunoglobulin E / immunology
  • Immunoglobulin G / blood*
  • Infant
  • Male
  • Middle Aged
  • Milk Hypersensitivity / diagnosis*
  • Milk Hypersensitivity / immunology
  • Milk Proteins / immunology*
  • Protein Binding / immunology
  • Young Adult


  • Allergens
  • Epitopes
  • Immunoglobulin A
  • Immunoglobulin G
  • Milk Proteins
  • Immunoglobulin E
  • Complement System Proteins