title: Identification of novel peptide biomarkers to predict safety and efficacy of cow's milk oral immunotherapy by peptide microarray.
abstract: BACKGROUND
  Cow's milk oral immunotherapy (CM-OIT) is still an experimental treatment. The development of novel biomarkers to predict the safety and efficacy of CM-OIT is crucial to translate this treatment to common clinical practice.
  
  
  OBJECTIVE
  To analyse long-term changes in IgE and IgG4 epitope binding profile induced by CM-OIT to identify safety and efficacy biomarkers.
  
  
  METHODS
  We studied 25 CM-allergic children who underwent CM-OIT and seven non-treated CM-allergic children as controls. CM-OIT patients were classified as low, moderate, and high risk according to the number of allergic reactions (safety), time required to achieve desensitization (efficacy) and need of premedication. IgE and IgG4 peptide microarray immunoassay was performed using a library of overlapping peptides of CM proteins at baseline, after oral desensitization, and 6, 12, and 24 months of follow-up.
  
  
  RESULTS
  Cow's milk oral immunotherapy induced a rapid increase of IgG4-binding epitopes and a slow decrease in IgE-binding epitopes. High-risk patients recognized a statistically significant higher number of IgE peptides in caseins at all the times studied. Similar but less pronounced changes were observed for IgG4-positive peptides. Clustering analysis grouped together the high-risk patients, and we identified 13 regions of caseins significantly differed between groups of patients. Bioinformatics analysis selected two sets of 16 IgE-binding peptides at baseline that predicted safety (R(2)  = 0.858) and efficacy (R(2)  = 0.732), respectively, of CM-OIT.
  
  
  CONCLUSIONS
  We found two sets of IgE-binding peptides that can be used as novel biomarkers to predict the safety and efficacy of CM-OIT before starting treatment.
authors.affiliation: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.|CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Botas
authors.affiliation: Servicio de Alergología, Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Álvarez
authors.affiliation: Servicio de Alergología, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Cerecedo
authors.affiliation: Servicio de Alergología, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Vlaicu
authors.affiliation: Servicio de Alergología, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Diéguez
authors.affiliation: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.|CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Gómez-Coronado
authors.affiliation: Servicio de Alergología, Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Rivas
authors.affiliation: Servicio de Alergología, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: de la Hoz
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers; D002364:Caseins / Q000737:chemistry / Q000276:immunology; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D019295:Computational Biology; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008892:Milk / Q000009:adverse effects*; D016269:Milk Hypersensitivity / Q000175:diagnosis* / Q000628:therapy*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011379:Prognosis; D011485:Protein Binding / Q000276:immunology
chemical_list: D015415:Biomarkers; D002364:Caseins; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides; D007073:Immunoglobulin E
keywords: IgE; IgG4; biomarker; cow's milk allergy; microarray; oral immunotherapy; peptide