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

Komei Ito1*, Masaki Futamura12, Robert Movérare34, Akira Tanaka5, Tsutomu Kawabe6, Tatsuo Sakamoto7 and Magnus P Borres38

Author Affiliations

1 Department of Allergy, Aichi Children's Health and Medical Center, Obu, Japan

2 Division of Allergy, National Center for Child Health and Development, Tokyo, Japan

3 Phadia AB (now Thermo Fisher Scientific), Uppsala, Sweden

4 Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden

5 Phadia KK (now Thermo Fisher Scientific), Tokyo, Japan

6 Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan

7 Department of Hygiene, Yamaguchi University Graduate School of Medicine, Ube, Japan

8 Department of Pediatrics, Sahlgrenska Academy of Göteborg University, Göteborg, Sweden

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Clinical and Molecular Allergy 2012, 10:1  doi:10.1186/1476-7961-10-1

Published: 2 January 2012



Cow'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.


Eighty-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).


The 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.


High 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.

casein; cow's milk allergy; IgE; IgG4; ImmunoCAP