title: Contribution of IgE and immunoglobulin free light chain in the allergic reaction to cow's milk proteins.
abstract: 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.
authors.affiliation: Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Schouten
authors.forename: Betty C A M
authors.initials: BC
authors.lastname: van Esch
authors.forename: Anders O J
authors.initials: AO
authors.lastname: van Thuijl
authors.forename: Bart R J
authors.initials: BR
authors.lastname: Blokhuis
authors.forename: Tom
authors.initials: T
authors.lastname: Groot Kormelink
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Hofman
authors.forename: Guido E
authors.initials: GE
authors.lastname: Moro
authors.forename: Günther
authors.initials: G
authors.lastname: Boehm
authors.forename: Sertac
authors.initials: S
authors.lastname: Arslanoglu
authors.forename: Aline B
authors.initials: AB
authors.lastname: Sprikkelman
authors.forename: Linette E M
authors.initials: LE
authors.lastname: Willemsen
authors.forename: Léon M J
authors.initials: LM
authors.lastname: Knippels
authors.forename: Frank A
authors.initials: FA
authors.lastname: Redegeld
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
mesh_terms: 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*
chemical_list: D002364:Caseins; D007147:Immunoglobulin Light Chains; D007073:Immunoglobulin E