The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children

Abstract

BackgroundCow's milk allergy is one of the most common food allergies among younger children. We investigated IgE antibodies to milk, and IgE and IgG4 antibodies to casein, α-lactalbumin and β-lactoglobulin in cow's milk allergic (CMA) and non-allergic (non-CMA) children in order to study their clinical usefulness.MethodsEighty-three children with suspected milk allergy (median age: 3.5 years, range: 0.8-15.8 years) were diagnosed as CMA (n = 61) or non-CMA (n = 22) based on an open milk challenge or convincing clinical history. Their serum concentrations of allergen-specific (s) IgE and IgG4 antibodies were measured using ImmunoCAP®. For the sIgG4 analysis, 28 atopic and 31 non-atopic control children were additionally included (all non-milk sensitized).ResultsThe CMA group had significantly higher levels of milk-, casein- and β-lactoglobulin-sIgE antibodies as compared to the non-CMA group. The casein test showed the best discriminating performance with a clinical decision point of 6.6 kUA/L corresponding to 100% specificity. All but one of the CMA children aged > 5 years had casein-sIgE levels > 6.6 kUA/L. The non-CMA group had significantly higher sIgG4 levels against all three milk allergens compared to the CMA group. This was most pronounced for casein-sIgG4 in non-CMA children without history of previous milk allergy. These children had significantly higher casein-sIgG4 levels compared to any other group, including the non-milk sensitized control children.ConclusionsHigh levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.

Human Allergen-Specific IgG Subclass Antibodies Measured Using ImmunoCAP Technology

“…The antibody response to BLG from milk in healthy, nonmilk-allergic adults was characterized by relatively low levels of pan IgG antibodies, which mainly belonged to the IgG4 subclass, and with a large interindividual vari- The relatively high serum levels of IgG4 to BLG shown in the present study have also been indicated in previous studies [20,21] . It is probably a consequence of repeated exposure to the antigen due to milk consumption leading to a strong IgG4 subclass antibody response in these tolerant individuals [7,8] .…”

“…Studies in the area of food allergy have reported different findings and, whilst foodspecific IgG4 has been shown to increase during successful oral immunotherapy [22,23] , there are conflicting data on whether or not specific IgG4 is higher in children with food allergy compared to nonallergic children. Recent data suggest that antibody responses may vary with the allergen, dose, and timing of exposure [20,[24][25][26] . Most studies on specific serum IgG responses to food proteins have investigated responses to egg, milk, and wheat proteins, which are 3 of the "big eight" food allergens, i.e.…”

Ingestion of Casein Hydrolysate Induces Oral Tolerance and Suppresses Subsequent Epicutaneous Sensitization and Development of Anaphylaxis Reaction to Casein in Mice

“…In addition, many researchers have focused on β-LG with regard to oral tolerance induction [6-9]. However, in clinical practice, it is reported that casein, rather than β-LG, is the more dominant causal allergen in CMA [10, 11]. Casein is contained in various processed foods such as infant formulas; therefore, it is important to investigate the immunological properties of casein in these foodstuffs.…”

Allergen Component Testing in the Diagnosis of Food Allergy

“…However, for those with Bos d 8 levels lower than the 95 % CDP, a high number of false negatives were observed, suggesting that an OFC should still be performed in these patients. In a study by Ito et al [11], investigators measured serum sIgE to CM extract and CM components in 83 children with suspected CM allergy, 61 diagnosed as allergic and 23 as non-allergic based on results of an open OFC or a convincing history. The CM allergic group showed higher levels of CM, Bos d 8, and betalactoglobulin (Bos d 5) sIgE than the non-allergic group.…”