title: Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes.
abstract: BACKGROUND
  The dynamics and balance of allergen-specific IgE, IgG4, and IgA binding might contribute to the development of tolerance in patients with cow's milk allergy (CMA). Profiling of antibody binding to cow's milk (CM) protein epitopes might help in predicting the natural history of allergy.
  
  
  OBJECTIVE
  We sought to investigate differences in IgE, IgG4, and IgA binding to CM epitopes over time between patients with early recovery or with persisting CMA.
  
  
  METHODS
  We studied serum samples at the time of diagnosis (mean age, 7 months), 1 year later, and at follow-up (mean age, 8.6 years) from 11 patients with persisting IgE-mediated CMA at age 8 to 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 5 major CM 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 CMA, 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 and that of IgE decreased over time. IgE and IgG4 binding to a panel of alpha(s1)-, alpha(s2)-, beta-, and kappa-casein regions predicted outcome with significant accuracy.
  
  
  CONCLUSIONS
  Attaining tolerance to CM is associated with decreased epitope binding by IgE and a concurrent increase in corresponding epitope binding by IgG4.
authors.affiliation: Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Savilahti
authors.forename: Ville
authors.initials: V
authors.lastname: Rantanen
authors.forename: Jing S
authors.initials: JS
authors.lastname: Lin
authors.forename: Sirkku
authors.initials: S
authors.lastname: Karinen
authors.forename: Kristiina M
authors.initials: KM
authors.lastname: Saarinen
authors.forename: Marina
authors.initials: M
authors.lastname: Goldis
authors.forename: Mika J
authors.initials: MJ
authors.lastname: Mäkelä
authors.forename: Sampsa
authors.initials: S
authors.lastname: Hautaniemi
authors.forename: Erkki
authors.initials: E
authors.lastname: Savilahti
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Sampson
mesh_terms: D000818:Animals; D002364:Caseins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D002648:Child; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D016269:Milk Hypersensitivity / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D011379:Prognosis; D011485:Protein Binding
chemical_list: D002364:Caseins; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D007073:Immunoglobulin E
references.citation: J Allergy Clin Immunol. 2008 Nov;122(5):977-983.e1
references.pmid: 18851876
references.citation: J Allergy Clin Immunol. 2005 Oct;116(4):893-9
references.pmid: 16210066
references.citation: J Allergy Clin Immunol. 2008 Dec;122(6):1154-60
references.pmid: 18951617
references.citation: J Allergy Clin Immunol. 2005 Oct;116(4):869-75
references.pmid: 16210063
references.citation: J Allergy Clin Immunol. 2007 Nov;120(5):1172-7
references.pmid: 17935766
references.citation: Ann Allergy Asthma Immunol. 2004 Nov;93(5 Suppl 3):S2-11
references.pmid: 15562868
references.citation: Clin Exp Allergy. 2001 Oct;31(10):1599-606
references.pmid: 11678861
references.citation: Clin Exp Allergy. 2007 Jun;37(6):831-8
references.pmid: 17517096
references.citation: Clin Exp Allergy. 2000 Mar;30(3):400-6
references.pmid: 10691899
references.citation: J Allergy Clin Immunol. 2009 Aug;124(2):292-300, 300.e1-97
references.pmid: 19577283
references.citation: J Immunol. 2004 Mar 1;172(5):3252-9
references.pmid: 14978133
references.citation: Clin Exp Allergy. 2010 Feb;40(2):251-6
references.pmid: 19958365
references.citation: J Allergy Clin Immunol. 2002 Aug;110(2):293-7
references.pmid: 12170271
references.citation: J Allergy Clin Immunol. 2008 May;121(5):1120-1125.e2
references.pmid: 18374405
references.citation: Clin Exp Allergy. 2007 Sep;37(9):1277-85
references.pmid: 17845407
references.citation: J Allergy Clin Immunol. 1999 Aug;104(2 Pt 1):457-61
references.pmid: 10452771
references.citation: Clin Exp Allergy. 2007 Jul;37(7):1103-10
references.pmid: 17581206
references.citation: J Allergy Clin Immunol. 2009 Aug;124(2):315-22, 322.e1-3
references.pmid: 19577281
references.citation: J Allergy Clin Immunol. 2008 Sep;122(3):589-94
references.pmid: 18774394
references.citation: J Immunol. 2007 Apr 1;178(7):4658-66
references.pmid: 17372025
references.citation: Biotechnol Adv. 2005 Sep;23(6):423-9
references.pmid: 15978770
references.citation: Genes Immun. 2009 Mar;10(2):112-9
references.pmid: 18923431
references.citation: Clin Exp Allergy. 2002 Sep;32(9):1293-8
references.pmid: 12220466
references.citation: J Immunol. 1999 Sep 1;163(5):2944-52
references.pmid: 10453043
references.citation: J Pediatr. 2004 Feb;144(2):218-22
references.pmid: 14760265
references.citation: Nat Biotechnol. 2008 Sep;26(9):1011-3
references.pmid: 18779814
references.citation: Allergy. 1990 Nov;45(8):587-96
references.pmid: 2288394
references.citation: J Allergy Clin Immunol. 2008 Aug;122(2):342-7, 347.e1-2
references.pmid: 18620743
references.citation: J Allergy Clin Immunol. 2003 Nov;112(5):915-22
references.pmid: 14610480