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Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy - 18/04/17

Doi : 10.1016/j.jaci.2016.04.024 
Marcel Frick, MS a, b, , Jörg Fischer, MD c, , Arthur Helbling, MD d, Franziska Ruëff, MD e, Dorothea Wieczorek, MD f, Markus Ollert, MD g, h, Wolfgang Pfützner, MD i, Sabine Müller, MD b, Johannes Huss-Marp, MD, MBA b, Britta Dorn a, b, Tilo Biedermann, MD c, j, Jonas Lidholm, PhD k, Gerta Ruecker, PhD l, Frank Bantleon, PhD m, Michaela Miehe, PhD m, Edzard Spillner, PhD m, , Thilo Jakob, MD a, b, ,
a Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Justus Liebig University, Gießen, Germany 
b Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany 
c Department of Dermatology and Allergology, University Medical Center Tübingen, Tübingen, Germany 
d Department of Internal Medicine, Spital Netz Bern, Allergy Unit Zieglerspital, Bern, Switzerland 
e Department of Dermatology and Allergology, Ludwig-Maximilian-University Munich, Munich, Germany 
f Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany 
g Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg 
h Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark 
i Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Philipps University, Marburg, Germany 
j Department of Dermatology and Allergology, Technical University Munich, Munich, Germany 
k Thermo Fisher Scientific, Uppsala, Sweden 
l Institute for Medical Biometry and Statistics, Medical Center - University of Freiburg, Freiburg, Germany 
m Department of Engineering, Aarhus University, Immunological Engineering, Aarhus, Denmark 

Corresponding author: Thilo Jakob, MD, Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Justus Liebig University Gießen, Gaffkystr. 14, 35395 Gießen, Germany.Department of Dermatology and AllergologyUniversity Medical Center Gießen-MarburgJustus Liebig University GießenGaffkystr. 14Gießen35395Germany

Abstract

Background

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.

Objective

We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome.

Methods

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.

Results

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 sIgG4 induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable.

Conclusions

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.

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Graphical abstract




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Key words : Apis mellifera, Hymenoptera venom allergy, HBV allergy, recombinant allergen, allergen-specific immunotherapy, treatment failure

Abbreviations used : AUC, HBV, HB, LOD, NLR, OR, PLR, ROC, sIgE, VIT


Plan


 This work was supported in part by a research grant of Thermo Fisher Scientific, Freiburg, to T.J.
 Disclosure of potential conflict of interest: F. Ruëff has worked as an adviser for ALK Abelló Arzneimittel GmbH, Bencard, DST GmbH, and Dr. Gerhard Mann chem.-pharm. Fabrik GmbH; has received speaker's honorarium from ALK-Abelló Arzneimittel GmbH, Astra Zeneca, Bencard, Novartis Pharma GmbH, HAL, MEDA Pharma GmbH & Co, Semperit Technische Produkte Gesellschaft m.b.H, and Stallergenes GmbH; has received consultancy fees from Novartis, HAL, and ALK-Abelló; and has received research support from Novartis. M. Ollert has received consultancy fees from Siemens Healthcare and Hitachi Chemical Diagnostics; has received lecture fees from ThermoFisher-Phadia and Siemens Healthcare; has stock/stock options in Siemens Healthcare; and is Scientific Cofounder of the University biotech spin-off enterprise Protein-Ligand-Structural-Design (PLS-Design) GmbH, Hamburg, Germany (2004). W. Pfützner has received consultancy fees from ALK-Abelló as an advisory board member; has received research support from the Deutsche Forschungsgemeinschaft (DFG), Philipps University Marburg, and the University Clinic of Marburg; has received lecture fees from ALK-Abelló and Novartis; has received research support from Phadia/Thermo Fisher Scientific, Freiburg, Germany. S. Müller has received lecture fees from Novartis, ALK-Abelló, and Bencard. J. Huss-Marp has been employed by, has received lecture fees from, and has stock/stock options in Phadia GmbH, ThermoFisher Scientific. T. Biedermann has received research funding and speaker's honorarium from Phadia/Thermo Fisher Scientific, Freiburg; has received consultancy fees from Phadia and ThermoFisher; has received research support from DFG, Novartis, Phadia, and ThermoFisher; and has received lecture fees from MSD, Novartis, HIPP GmbH & Co, ALK-Abelló Arzneimittel GmbH, MedComms Ltd, and Astellas Pharma GmbH. J. Lidholm is an employee of Thermo Fisher Scientific, manufacturer of the assay system used in the study. E. Spillner is cofounder of PLS-Design GmbH, Hamburg, Germany. T. Jakob has received research support, consultancy fees, and travel support from Thermo Fisher Scientific; is on the Germany Society of Allergy and Clinical Immunology Board; has received consultancy fees from ALK-Abelló, Allergy Therapeutics, Novartis, Leti GmbH, Stallergenes, and Allergopharma; is employed as Editor for Allergó Journal International, Springer, Germany; and has received lecture fees from ALK-Abello, Allergy Therapeutics, Novartis, Allergopharma, Stallergenes, and Thermo Fisher Scientific. The rest of the authors declare that they have no relevant conflicts of interest.


© 2016  The Authors. Publié par Elsevier Masson SAS. Tous droits réservés.
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