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

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 alpha S1-casein, alpha S2-casein, beta-casein, kappa-casein, alpha-lactalbumin, and beta-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 alpha S1-casein, alpha S2-casein, beta-casein, kappa-casein, and alpha-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.