title: Casein-specific immunoglobulins in cow's milk allergic patient subgroups reveal a shift to IgA dominance in tolerant patients.
abstract: Differences in casein-specific immunoglobulin (Ig) G-subclass and IgA serum levels between reactive and tolerant patients may hint at the immunopathogenesis during tolerance development in cow's milk allergy (CMA). alpha-, beta- and kappa-casein-specific IgG(1), IgG(4), IgE and IgA serum levels were compared in clinically reactive and tolerized IgE-mediated (n = 15) and non-IgE-mediated (n = 14) CMA with delayed gastrointestinal symptoms, using enzyme-linked immunosorbent assay (ELISA) and immunoblot techniques. The median anti-casein IgE levels in clinically reactive IgE-mediated CMA patients (n = 9) were 140- to 180-fold higher than in tolerized patients (n = 6) and 160- to 200-fold higher than in controls (n = 10). Median alpha-, beta- and kappa-casein-specific IgG(1) and IgG(4) levels were nine- to 60-fold higher in reactive patients and five- to 60-fold in tolerized patients. Clinical tolerance in IgE-mediated CMA was thus associated with decreased casein-specific IgE, IgG(4) and IgG(1), whereas serum IgA anti-alpha -, beta- and kappa-casein remained practically unaltered. Tolerized cow's milk protein (CMP)-sensitive atopic dermatitis had, in particular, decreased kappa-casein-specific IgG(1) levels, compared with clinically reactive patients. The ELISA levels to immunoblot correlation profile for the alpha-, beta- and kappa-casein-specific IgE suggested that the IgE-mediated CMA patients predominantly reacted to tertiary alpha- and beta-casein epitopes whereas the IgE in non-IgE-mediated patients reacted to linearized alpha-, beta- and kappa-casein epitopes. Clinical tolerance in non-IgE-mediated CMA patients (n = 9) was associated with a four- to 10-fold decrease in casein-specific IgE levels, accompanied by a five- to eightfold decrease in IgG(1) and five- to 60-fold decrease in IgG(4) levels, whereas casein-specific IgA levels remained unaltered. Thus, tolerance in both patient groups was characterized by a generalized decreased humoral immune response to caseins, which induced a functional shift to IgA dominance.
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; D000818:Animals; D000918:Antibody Specificity; D002364:Caseins / Q000276:immunology*; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D015151:Immunoblotting / Q000379:methods; D016056:Immunodominant Epitopes / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D016269:Milk Hypersensitivity / Q000175:diagnosis / Q000276:immunology*
chemical_list: D002364:Caseins; D016056:Immunodominant Epitopes; D007070:Immunoglobulin A; D007073:Immunoglobulin E