TY - JOUR
T1 - Contribution of IgE and immunoglobulin free light chain in the allergic reaction to cow's milk proteins
AU - Schouten, Bastiaan
AU - van Esch, Betty C. A. M.
AU - van Thuijl, Anders O. J.
AU - Blokhuis, Bart R. J.
AU - Kormelink, Tom Groot
AU - Hofman, Gerard A.
AU - Moro, Guido E.
AU - Boehm, Gunther
AU - Arslanoglu, Sertac
AU - Sprikkelman, Aline B.
AU - Willemsen, Linette E. M.
AU - Knippels, Leon M. J.
AU - Redegeld, Frank A.
AU - Garssen, Johan
PY - 2010/6
Y1 - 2010/6
N2 - 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. (J Allergy Clin Immunol 2010;125:1308-14.)
AB - 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. (J Allergy Clin Immunol 2010;125:1308-14.)
KW - Immunoglobulin free light chains
KW - IgE
KW - cow's milk allergy
KW - food allergy
KW - casein
KW - whey
KW - atopic dermatitis
KW - ATOPIC-DERMATITIS
KW - FOOD ALLERGY
KW - INFLAMMATORY DISEASES
KW - CLINICAL TOLERANCE
KW - SCORAD INDEX
KW - MAST-CELLS
KW - HYPERSENSITIVITY
KW - CHILDREN
KW - SERUM
KW - WHEY
U2 - 10.1016/j.jaci.2010.02.039
DO - 10.1016/j.jaci.2010.02.039
M3 - Article
SN - 0091-6749
VL - 125
SP - 1308
EP - 1314
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -