Contribution of IgE and immunoglobulin free light chain in the allergic reaction to cow's milk proteins.
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.


OBJECTIVE
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.
Schouten
Bastiaan
B
Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
van Esch
Betty C A M
BC
van Thuijl
Anders O J
AO
Blokhuis
Bart R J
BR
Groot Kormelink
Tom
T
Hofman
Gerard A
GA
Moro
Guido E
GE
Boehm
Günther
G
Arslanoglu
Sertac
S
Sprikkelman
Aline B
AB
Willemsen
Linette E M
LE
Knippels
Léon M J
LM
Redegeld
Frank A
FA
Garssen
Johan
J
D000818:Animals; D002364:Caseins / Q000276:immunology*; D002417:Cattle; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000097:blood / Q000276:immunology*; D007223:Infant; D051379:Mice; D008809:Mice, Inbred C3H; D016269:Milk Hypersensitivity / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*
D002364:Caseins; D007147:Immunoglobulin Light Chains; D007073:Immunoglobulin E