title: Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy.
abstract: Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which have been reported to be underrepresented in therapeutic HBV preparations.
  
  
  
  We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome.
  
  
  
  HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge.
  
  
  
  No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG4induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable.
  
  
  
  Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy.
authors.affiliation: Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Justus Liebig University, Gießen, Germany; Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Frick
authors.affiliation: Department of Dermatology and Allergology, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Department of Internal Medicine, Spital Netz Bern, Allergy Unit Zieglerspital, Bern, Switzerland.
authors.forename: Arthur
authors.initials: A
authors.lastname: Helbling
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian-University Munich, Munich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Ruëff
authors.affiliation: Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Wieczorek
authors.affiliation: Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark.
authors.forename: Markus
authors.initials: M
authors.lastname: Ollert
authors.affiliation: Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Philipps University, Marburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pfützner
authors.affiliation: Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Müller
authors.affiliation: Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Huss-Marp
authors.affiliation: Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Justus Liebig University, Gießen, Germany; Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Dorn
authors.affiliation: Department of Dermatology and Allergology, University Medical Center Tübingen, Tübingen, Germany; Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
authors.affiliation: Thermo Fisher Scientific, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Lidholm
authors.affiliation: Institute for Medical Biometry and Statistics, Medical Center - University of Freiburg, Freiburg, Germany.
authors.forename: Gerta
authors.initials: G
authors.lastname: Ruecker
authors.affiliation: Department of Engineering, Aarhus University, Immunological Engineering, Aarhus, Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Bantleon
authors.affiliation: Department of Engineering, Aarhus University, Immunological Engineering, Aarhus, Denmark.
authors.forename: Michaela
authors.initials: M
authors.lastname: Miehe
authors.affiliation: Department of Engineering, Aarhus University, Immunological Engineering, Aarhus, Denmark.
authors.forename: Edzard
authors.initials: E
authors.lastname: Spillner
authors.affiliation: Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Justus Liebig University, Gießen, Germany; Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany. Electronic address: thilo.jakob@derma.med.uni-giessen.de.
authors.forename: Thilo
authors.initials: T
authors.lastname: Jakob
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D001514:Bee Venoms / Q000276:immunology / Q000627:therapeutic use*; D002648:Child; D003429:Cross Reactions; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000485:Allergens; C569170:Api m 10 allergen, Apis mellifera; D001514:Bee Venoms; D007073:Immunoglobulin E
keywords: Apis mellifera; HBV allergy; Hymenoptera venom allergy; allergen-specific immunotherapy; recombinant allergen; treatment failure