Maintenance of tolerance to cow's milk in atopic individuals is characterized by high levels of specific immunoglobulin G4 (original) (raw)
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Differences between normal and milk allergic subjects in their immune responses after milk ingestion
Archives of Disease in Childhood, 1983
In order to understand why non-atopic people do not have adverse symptoms to food antigens which enter the circulation after eating, 8 non-atopic and 10 atopic eczema- and milk-allergic subjects were challenged with milk, and the types of circulating immune complexes formed were analysed. Although the amount of beta-lactoglobulin incorporated into complexes did not differ statistically between the groups, the type of immune complex did. Of the non-atopic individuals, 5 formed IgA and 2 IgG complexes. Of the milk-allergic group, all showed a rise in at least one type; 5 formed IgA, 7 IgG, 6 IgE, and 6 formed C1q-binding complexes. Our data suggest that serum IgA is concerned in safe food antigen handling in non-atopic people, and that the differences in the type of immune complexes formed in response to antigen challenge may underlie the systemic symptoms of food allergy.
Journal of Allergy and Clinical Immunology, 2010
Background-Dynamics and balance of allergen specific IgE, IgG4 and IgA binding may contribute to the development of tolerance in cow's milk allergy. Profiling of antibody binding to cow's milk protein epitopes may help in predicting natural history of allergy. Objective-To investigate differences in IgE, IgG4 and IgA binding to cow's milk epitopes over time between patients with early recovery or with persisting cow's milk allergy. Methods-We studied serum samples at the time of diagnosis (mean age 7 months), one year later and at follow-up (mean age 8.6 years) from 11 patients with persisting IgE-mediated cow's milk allergy at age 8-9 years, and 12 patients who recovered by age 3 years. We measured the binding of IgE, IgG4 and IgA antibodies to sequential epitopes derived from five major cow's milk proteins with a peptide microarray-based immunoassay. We analyzed the data with a novel image processing method together with machine learning prediction. Results-IgE epitope binding patterns were stable over time in patients with persisting cow's milk allergy, whereas binding decreased in patients who recovered early. Binding patterns of IgE and IgG4 overlapped. Among patients who recovered early, the signal of IgG4 binding increased while that of IgE decreased over time. IgE and IgG4 binding to a panel of αs1-, αs2-, β-and κcasein regions predicted outcome with significant accuracy. Conclusions-Attaining tolerance to cow's milk is associated with decreased epitope binding by IgE and a concurrent increase in corresponding epitope binding by IgG4.
Allergy, 2011
The first adverse reactions to cow's milk were already described 2000 years ago. However, it was only 50 years ago that several groups started with the analysis of cow's milk allergens. Meanwhile the spectrum of allergy eliciting proteins within cow's milk is identified and several cow's milk allergens have been characterized regarding their biochemical properties, fold and IgE binding epitopes. The diagnosis of cow's milk allergy is diverse ranging from fast and cheap in vitro assays to elaborate in vivo assays. Considerable effort was spent to improve the diagnosis from an extract-based into a component resolved concept. There is still no suitable therapy available against cow's milk allergy except avoidance. Therefore research needs to focus on the development of suitable and safe immunotherapies that do not elicit severe side effect.
Development of natural tolerance and induced desensitization in cow’s milk allergy
Pediatric Allergy and Immunology, 2013
Background: Oral immunotherapy (OIT) with cow's milk (CM) has been reported to induce a number of specific antibody responses, but these remain to be fully characterized. Our objective was to explore whether IgE and IgG4 epitope binding profiles could predict the risk of side effects during CM OIT. Methods: The study population consisted of 32 children (6-17 yr of age) with CM allergy: 26 children who successfully completed OIT and six children who discontinued therapy due to adverse reactions. We investigated sera drawn before and after OIT. We analyzed specific IgE and IgG4 binding to CM protein-derived peptides with a microarray-based immunoassay. Antibody binding affinity was analyzed with a competition assay where CM proteins in solution competed with peptides printed on the microarray. Results: IgE binding to CM peptides decreased and IgG4 binding increased following the OIT in children who attained desensitization. Compared with children who successfully completed OIT, those who discontinued OIT due to adverse reactions developed increased quantities and affinity of epitope-specific IgE antibodies and a broader diversity of IgE and IgG4 binding, but less overlap in IgE and IgG4 binding to CM peptides. Conclusions: Detailed analysis of IgE and IgG4 binding to CM peptides may help in predicting whether CM OIT will be tolerated successfully. It may thus improve the safety of the therapy.
Allergenicity of major cow's milk and peanut proteins determined by IgE and IgG immunoblotting
Allergy, 2000
Background: Speci®c IgG antibodies are frequently observed in food-allergic patients. However, the allergen-fraction speci®city of IgG antibodies in relation to IgE antibodies is not well de®ned. Our aim was to determine the IgE and IgG antibody pro®le to major cow's milk and peanut-antigen fractions in foodallergic patients and tolerant individuals. Methods: Sera were collected from 10 patients allergic to cow's milk and 10 patients allergic to peanuts, as well as from 20 control subjects. Cow's milk and peanut proteins were migrated on SDS±PAGE and immunoblotted for IgE, IgG, and IgG4 antibodies. Food-speci®c IgE concentrations were measured by CAP System FEIA 2 , and IgG and IgG4 concentrations by ELISA. Results: In food-allergic children, similar fraction-speci®c IgE, IgG, and IgG4 antibody-binding pro®les to the major cow's milk or peanut antigens were found. In nonallergics, the presence of fraction-speci®c IgG antibodies was mostly dependent on regular ingestion of the food. The presence of speci®c antibody on immunoblots correlated with their quantitative measurement. The mean value for speci®c IgE in cow's milk-allergic patients was 450t1326 IU/ml, and 337t423 IU/ml in peanut-allergic patients. Speci®c IgG antibody values in milkallergic patients were not different (median OD 1.5, range 0.3±2.3) from controls (median OD 1, range 0.2±1.8). However, in peanut-allergic patients, IgG concentrations were signi®cantly higher than in controls (OD 1.2 [0.5±1.3] vs 0.5 [0.3±0.7]; P<0.01). Conclusions: Similar fraction-speci®c IgE and IgG antibody pro®les in allergic individuals suggest a common switching trigger involving both isotypes. Intrinsic allergenicity might explain identical IgG antibody fraction speci®city in nonallergics and in allergics. The presence of IgG antibodies in nonallergics was related to regular ingestion of the food.
Clinical & Experimental Allergy, 2011
Background Serum and secretory IgA concentrations have been suggested to be inversely associated with allergic symptoms in children. Furthermore, low maternal milk IgA concentration has been suggested to be associated with the development of cow's milk allergy. Objective Our aim was to explore whether the serum IgA concentrations in infancy and the IgA concentration of maternal milk predict atopic manifestations in childhood and up to age 20 years. Methods A cohort of 200 unselected full-term newborns was prospectively followed up from birth to age 20 years with measurement of serum total IgA at ages 2 and 6 months. The mothers were encouraged to maintain exclusive breastfeeding for as long as possible. Total IgA concentration of maternal milk was measured at birth (colostrum, n = 169) and at 2 (n = 167) and 6 (n = 119) months of lactation. The children were re-assessed at ages 5, 11 and 20 years for the occurrence of allergic symptoms, with skin prick testing and measurement of serum IgE. Results Children and adolescents with respiratory allergic symptoms and sensitization had a higher serum IgA concentration at age 2 months than the non-atopic subjects. Colostrum and breast milk IgA concentrations were not associated with the development of allergic symptoms in the recipient infant. However, maternal milk IgA concentration at 6 months of lactation was inversely associated with elevated serum total IgE and positive skin prick test to tree pollen in the offspring at age 20 years. Conclusions and Clinical Relevance Increased serum IgA concentration at age 2 months is associated with the development of subsequent allergic symptoms and sensitization in childhood and adolescence. Maternal milk IgA concentrations are not associated with subsequent allergic symptoms in the recipient infant. The present study provides novel information on the role of IgA in the development of respiratory allergy and sensitization.