Background: Cow's milk allergy (CMA) affects 2.5% of young infants. In previous murine studies it was observed that allergic sensitization to the major cow's milk allergens casein and whey led, respectively, to IgE-independent and IgE-dependent clinical responses. Objectives: In this study the involvement of immunoglobulin free light chains (Ig-fLCs) in the hypersensitivity response to cow's milk proteins was explored in mice, and Ig-fLC serum levels were determined in children affected by CMA or atopic dermatitis (AD). Methods: Mice were orally sham, casein, or whey sensitized. Acute allergen-specific skin responses were determined, and serum immunoglobulin and Ig-fLC concentrations were measured. Ig-fLC dependency was validated by using the Ig-fLC blocker F991 in actively and passively sensitized mice. Ig-fLC serum concentrations were measured in a cohort of infants with CMA and infants with AD. Results: After sensitization, no specific IgE was detectable in sera of casein-sensitized mice, whereas specific IgE levels were enhanced in whey-sensitized mice. Instead, Ig-fLC levels were increased in sera from casein-sensitized mice. Furthermore, blocking Ig-fLCs strongly diminished the allergic skin responses not only in casein-sensitized mice but also in mice transferred with splenocyte supernatants of casein-sensitized mice. In both patients with CMA and patients with AD, serum Ig-fLC concentrations were significantly enhanced. Conclusions: This study indicates that sensitization with cow's milk proteins can lead to both IgE-dependent and Ig-fLC-dependent allergic hypersensitivity responses. Also, in children affected with CMA or AD, serum Ig-fLC concentrations were increased, implying the relevance of Ig-fLC measurements in the diagnoses of human allergic disease.

IgE, Immunoglobulin free light chains, atopic dermatitis, casein, cow's milk allergy, food allergy, whey,
Journal of Allergy and Clinical Immunology
Erasmus MC: University Medical Center Rotterdam

Schouten, B, van Esch, B.C.A.M, van Thuijl, A.O.J, Blokhuis, B.R.J, Groot Kormelink, T, Hofman, G.A, … Garssen, J. (2010). Contribution of IgE and immunoglobulin free light chain in the allergic reaction to cow's milk proteins. Journal of Allergy and Clinical Immunology, 125(6), 1308–1314. doi:10.1016/j.jaci.2010.02.039