Background: Methods for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy. Methods: We investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, β-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56). Results: Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p < 0.05). Adverse reactions in the entire population were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p < 0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased and IgE to CM decreased during OIT in children who achieved desensitization (p < 0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased significantly (p < 0.03) and CM IgE remained unchanged. Conclusions: High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization.

Saarinen KM, Juntunen-Backman K, Jarvenpaa AL, Kuitunen P, Lope L, Renlund M, et al: Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: a prospective study of 6209 infants. J Allergy Clin Immunol 1999;104:457-461.
Saarinen KM, Pelkonen AS, Makela MJ, Savilahti E: Clinical course and prognosis of cow's milk allergy are dependent on milk-specific IgE status. J Allergy Clin Immunol 2005;116:869-875.
Elizur A, Rajuan N, Goldberg MR, Leshno M, Cohen A, Katz Y: Natural course and risk factors for persistence of IgE-mediated cow's milk allergy. J Pediatr 2012;161:482-487.e1.
Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG: A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy 2004;59:980-987.
Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K: Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 2007;62:1261-1269.
Morisset M, Moneret-Vautrin DA, Guenard L, Cuny JM, Frentz P, Hatahet R, et al: Oral desensitization in children with milk and egg allergies obtains recovery in a significant proportion of cases. A randomized study in 60 children with cow's milk allergy and 90 children with egg allergy. Eur Ann Allergy Clin Immunol 2007;39:12-19.
Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, et al: A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol 2008;122:1154-1160.
Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, et al: Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol 2008;121:343-347.
Pajno GB, Caminiti L, Ruggeri P, De Luca R, Vita D, La Rosa M, et al: Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study. Ann Allergy Asthma Immunol 2010;105:376-381.
Martorell A, De la Hoz B, Ibanez MD, Bone J, Terrados MS, Michavila A, et al: Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy. Clin Exp Allergy 2011;41:1297-1304.
Alvaro M, Giner MT, Vazquez M, Lozano J, Dominguez O, Piquer M, et al: Specific oral desensitization in children with IgE-mediated cow's milk allergy. Evolution in one year. Eur J Pediatr 2012;171:1389-1395.
Vazquez-Ortiz M, Alvaro-Lozano M, Alsina L, Garcia-Paba MB, Piquer-Gibert M, Giner-Munoz MT, et al: Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test. Clin Exp Allergy 2013;43:92-102.
Salmivesi S, Korppi M, Makela MJ, Paassilta M: Milk oral immunotherapy is effective in school-aged children. Acta Paediatr 2013;102:172-176.
Skripak JM, Matsui EC, Mudd K, Wood RA: The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol 2007;120:1172-1177.
Savilahti EM, Saarinen KM, Savilahti E: Duration of clinical reactivity in cow's milk allergy is associated with levels of specific immunoglobulin G4 and immunoglobulin A antibodies to beta-lactoglobulin. Clin Exp Allergy 2010;40:251-256.
Savilahti EM, Rantanen V, Lin JS, Karinen S, Saarinen KM, Goldis M, et al: Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes. J Allergy Clin Immunol 2010;125:1315, 1321.e9.
Wang J, Lin J, Bardina L, Goldis M, Nowak-Wegrzyn A, Shreffler WG, et al: Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol 2010;125:695, 702, 702.e1-702.e6.
Shek LP, Soderstrom L, Ahlstedt S, Beyer K, Sampson HA: Determination of food specific IgE levels over time can predict the development of tolerance in cow's milk and hen's egg allergy. J Allergy Clin Immunol 2004;114:387-391.
Savilahti EM, Viljanen M, Kuitunen M, Savilahti E: Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low beta-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy. Pediatr Allergy Immunol 2012;23:590-596.
Savilahti EM, Saarinen KM, Savilahti E: Specific antibodies to cow's milk proteins in infants: effect of early feeding and diagnosis of cow's milk allergy. Eur J Nutr 2010;49:501-504.
Cerutti A, Rescigno M: The biology of intestinal immunoglobulin A responses. Immunity 2008;28:740-750.
Miranda DO, Silva DA, Fernandes JF, Queiros MG, Chiba HF, Ynoue LH, et al: Serum and salivary IgE, IgA, and IgG4 antibodies to Dermatophagoides pteronyssinus and its major allergens, Der p1 and Der p2, in allergic and nonallergic children. Clin Dev Immunol 2011;2011:302739.
Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, et al: Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol 2008;121:1120-1125.e2.
Pilette C, Nouri-Aria KT, Jacobson MR, Wilcock LK, Detry B, Walker SM, et al: Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. J Immunol 2007;178:4658-4666.
Saarinen KM, Vaarala O, Klemetti P, Savilahti E: Transforming growth factor-beta1 in mothers' colostrum and immune responses to cows' milk proteins in infants with cows' milk allergy. J Allergy Clin Immunol 1999;104:1093-1098.
Kim JS, Nowak-Wegrzyn A, Sicherer SH, Noone S, Moshier EL, Sampson HA: Dietary baked milk accelerates the resolution of cow's milk allergy in children. J Allergy Clin Immunol 2011;128:125-131.e2.
Bedoret D, Singh AK, Shaw V, Hoyte EG, Hamilton R, DeKruyff RH, et al: Changes in antigen-specific T-cell number and function during oral desensitization in cow's milk allergy enabled with omalizumab. Mucosal Immunol 2012;5:267-276.
Shamji MH, Ljorring C, Francis JN, Calderon MA, Larche M, Kimber I, et al: Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy 2012;67:217-226.
Shek LP, Bardina L, Castro R, Sampson HA, Beyer K: Humoral and cellular responses to cow's milk proteins in patients with milk-induced IgE-mediated and non-IgE-mediated disorders. Allergy 2005;60:912-919.
Meiler F, Klunker S, Zimmermann M, Akdis CA, Akdis M: Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and Toll-like receptors. Allergy 2008;63:1455-1463.
Kukkonen AK, Savilahti EM, Haahtela T, Savilahti E, Kuitunen M: Ovalbumin-specific immunoglobulins A and G levels at age 2 years are associated with the occurrence of atopic disorders. Clin Exp Allergy 2011;41:1414-1421.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.