title: Changes in humoral responses to beta-lactoglobulin in tolerant patients suggest a particular role for IgG4 in delayed, non-IgE-mediated cow's milk allergy.
abstract: The major cow's milk allergen beta-lactoglobulin (beta-LG) is relatively resistant to enzymatic degradation and may therefore be involved in non-immunoglobulin (Ig)E-mediated cow's milk allergy (CMA) with delayed gastrointestinal symptoms. Serum levels of beta-LG-specific IgG(1), IgG(4), IgE, and IgA were compared in clinically reactive and tolerized IgE-mediated and non-IgE-mediated CMA with delayed gastrointestinal symptoms (n = 29) and controls (n = 10). Tolerance was associated with decreased beta-LG-specific IgE, IgG(1), and IgG(4) levels in both patient groups. However, the significantly increased beta-LG-specific IgG(4) levels in clinically reactive non-IgE-mediated CMA patients, and its median 36-fold reduction in tolerant patients, suggested a possible immunopathological role for IgG(4) in delayed CMA. Similarly, the significantly increased beta-LG-specific IgE levels in IgE-mediated CMA patients were decreased 44-fold in tolerant patients. The tolerant patients had apparently shifted the humoral immune response from a beta-LG-specific IgE- and/or IgG(4)-dominated immune response to an IgA-dominated immune response as the IgA/IgE or IgA/IgG(4) ratios increased 90- and 15-fold in tolerant IgE-mediated-, and non-IgE-mediated CMA patients, respectively. Thus, the marked difference in beta-LG-specific Ig ratios suggested a tolerance-induced inhibition of a Th(2)-type of immune response with significantly increased IgA dominance in both CMA patient groups.
authors.affiliation: National Veterinary Institute, Oslo, Norway. gaynour-b.sletten@vetinst.no
authors.forename: Gaynour B G
authors.initials: GB
authors.lastname: Sletten
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Halvorsen
authors.forename: Eliann
authors.initials: E
authors.lastname: Egaas
authors.forename: Trond S
authors.initials: TS
authors.lastname: Halstensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood*; D007782:Lactoglobulins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008892:Milk / Q000009:adverse effects*; D016269:Milk Hypersensitivity / Q000097:blood* / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007782:Lactoglobulins; D007073:Immunoglobulin E