• cow's milk protein;
  • immunoglobulins

The major cow's milk allergen β-lactoglobulin (β-LG) is relatively resistant to enzymatic degradation and may therefore be involved in non-immunoglobulin (Ig)E-mediated cow's milk allergy (CMA) with delayed gastrointestinal symptoms. Serum levels of β-LG-specific IgG1, IgG4, IgE, and IgA were compared in clinically reactive and tolerized IgE-mediated and non-IgE-mediated CMA with delayed gastrointestinal symptoms (n = 29) and controls (n = 10). Tolerance was associated with decreased β-LG-specific IgE, IgG1, and IgG4 levels in both patient groups. However, the significantly increased β-LG-specific IgG4 levels in clinically reactive non-IgE-mediated CMA patients, and its median 36-fold reduction in tolerant patients, suggested a possible immunopathological role for IgG4 in delayed CMA. Similarly, the significantly increased β-LG-specific IgE levels in IgE-mediated CMA patients were decreased 44-fold in tolerant patients. The tolerant patients had apparently shifted the humoral immune response from a β-LG-specific IgE- and/or IgG4-dominated immune response to an IgA-dominated immune response as the IgA/IgE or IgA/IgG4 ratios increased 90- and 15-fold in tolerant IgE-mediated-, and non-IgE-mediated CMA patients, respectively. Thus, the marked difference in β-LG-specific Ig ratios suggested a tolerance-induced inhibition of a Th2-type of immune response with significantly increased IgA dominance in both CMA patient groups.