title: High IgE levels to α-lactalbumin, β-lactoglobulin and casein predict less successful cow's milk oral immunotherapy.
abstract: BACKGROUND
  A new treatment option for persistent cow's milk allergy (CMA) is oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG4 antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome.
  
  
  METHODS
  Seventy-six children (5-17 years) with challenge-verified CMA were subjected to a 6-month OIT protocol. The treatment aimed at reaching a maintenance dose of 200 ml CM (high dose = HD). Those who did not reach target were analysed as a low-dose (LD) group. Sera were characterized before and after OIT regarding serum levels of IgE and IgG4 to milk and five milk allergen components evaluated together with clinical CMA symptoms and outcome of OIT.
  
  
  RESULTS
  Fifty-five (72%) patients reached the maintenance dose (HD) during therapy. High specific IgE levels towards the milk allergens α-lactalbumin (P = 0.048), β-lactoglobulin (P = 0.006) and casein (P = 0.015) before OIT start were associated with lower maintenance dose reached. Patients who developed desensitization had a larger increase in IgG4 levels to α-lactalbumin (P = 0.034), β-lactoglobulin (P = 0.010), casein (P = 0.047) and lactoferrin (P = 0.030) during treatment than those who failed.
  
  
  CONCLUSIONS
  Component-resolved diagnostics before OIT can help to identify children with lower probability of a successful OIT outcome, as high IgE levels to α-lactalbumin, β-lactoglobulin and casein are associated with lower maintenance dose reached. An increase in the IgG4 concentration to milk components during treatment indicated effective desensitization.
authors.affiliation: Children's Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Kuitunen
authors.affiliation: Thermo Fisher Scientific, Uppsala, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Englund
authors.affiliation: Kuopio University Hospital, University of Eastern, Finland, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Remes
authors.affiliation: Thermo Fisher Scientific, Uppsala, Sweden.|Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Movérare
authors.affiliation: Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Pelkonen
authors.affiliation: Thermo Fisher Scientific, Uppsala, Sweden.|Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: M P
authors.initials: MP
authors.lastname: Borres
authors.affiliation: Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mäkelä
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002364:Caseins / Q000097:blood* / Q000276:immunology; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003888:Desensitization, Immunologic / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007167:Immunotherapy / Q000379:methods*; D007768:Lactalbumin / Q000097:blood* / Q000276:immunology; D008297:Male; D008892:Milk / Q000009:adverse effects / Q000276:immunology; D016269:Milk Hypersensitivity / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002364:Caseins; D007073:Immunoglobulin E; D007768:Lactalbumin
keywords: cow's milk allergy; desensitization; oral immunotherapy; specific IgE; specific IgG4