title: The degree of whey hydrolysis does not uniformly affect in vitro basophil and T cell responses of cow's milk-allergic patients.
abstract: BACKGROUND
  Several studies investigated whether hydrolysed proteins can induce tolerance to cow's milk (CM) in children at risk of developing CM allergy. Due to methodological problems and inconsistent findings, the evidence for a tolerogenic effect is limited. A major problem is that different hydrolysates may give different outcomes due to variations in their production and composition.
  
  
  OBJECTIVE
  The aim of the study was to investigate the effect of the degree of hydrolysis on the allergenicity and immunogenicity of whey hydrolysates.
  
  
  METHODS
  The hydrolysis of whey was stopped at different time-points between 1 and 60 min. In 18 CM allergic patients, the allergenicity of the hydrolysates was determined by immunoblot and the basophil activation test. To test immunogenicity, CM-specific T cell lines were generated.
  
  
  RESULTS
  In most patients, increasing time of hydrolysis decreased IgE recognition and basophil activation. However, in five patients, hydrolysed proteins induced more basophil activation than non-hydrolysed proteins. The immunoblot data indicated that these patients recognized either a 25- to 30-kDa degradation product of casein or a 10-kDa degradation product of whey. Although T cell activation was decreased in all patients over time, half of them still showed a positive response to the proteins after 60 min of hydrolysis.
  
  
  CONCLUSIONS
  Increasing the time of hydrolysis reduces both allergenicity and immunogenicity of whey hydrolysates in most but not all patients. This indicates that not the degree of hydrolysis is decisive but the presence and stability of IgE and T cell epitopes in the hydrolysate recognized by individual patients.
authors: Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: L A P M
authors: LA
authors: Meulenbroek
authors: S
authors: S
authors: Oliveira
authors: C F
authors: CF
authors: den Hartog Jager
authors: R J B
authors: RJ
authors: Klemans
authors: A F M
authors: AF
authors: Lebens
authors: T
authors: T
authors: van Baalen
authors: A C
authors: AC
authors: Knulst
authors: C A F M
authors: CA
authors: Bruijnzeel-Koomen
authors: J
authors: J
authors: Garssen
authors: L M J
authors: LM
authors: Knippels
authors: E
authors: E
authors: van Hoffen
mesh_terms: D000328:Adult; D000818:Animals; D001491:Basophils / Q000276:immunology*; D002417:Cattle; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008892:Milk / Q000009:adverse effects*; D016269:Milk Hypersensitivity / Q000276:immunology* / Q000378:metabolism*; D008894:Milk Proteins / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011492:Protein Hydrolysates / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D000067816:Whey Proteins; D055815:Young Adult
chemical_list: D008894:Milk Proteins; D010455:Peptides; D011492:Protein Hydrolysates; D000067816:Whey Proteins; D007073:Immunoglobulin E
keywords: T cells; allergenicity; basophils; cow's milk allergy; hydrolysed proteins; immunogenicity; infant formula