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Published in: Clinical and Translational Allergy 1/2018

Open Access 01-12-2018 | Research

Does clinical outcome of birch pollen immunotherapy relate to induction of blocking antibodies preventing IgE from allergen binding? A pilot study monitoring responses during first year of AIT

Authors: Sara Huber, Roland Lang, Markus Steiner, Lorenz Aglas, Fatima Ferreira, Michael Wallner, Thomas Hawranek, Gabriele Gadermaier

Published in: Clinical and Translational Allergy | Issue 1/2018

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Abstract

Background

The clinical benefit of allergen-specific immunotherapy (AIT) involves induction of blocking antibodies. It is not clear if these antibodies function via steric hindrance alone or a combination of levels, avidities, and epitope specificities, and clinical outcome cannot be predicted. We aim to in-depth characterize serum antibody profiles during birch pollen AIT, investigate therapy-induced antibodies for their capacity to block IgE binding to Bet v 1 and correlate data with clinical outcomes.

Methods

Immune responses of five birch pollen allergic patients were monitored during the first year of AIT by nasal provocation tests (NPTs), ImmunoCAP, immunoblots, direct and avidity enzyme-linked immunosorbent assays, mediator release assays, facilitated antigen binding (FAB) assays, and inhibition mediator release assays.

Results

There was no correlation between NPT results and therapy-induced changes in levels (IgE, IgG, IgA, IgM), avidities, or mediator release potency of Bet v 1-specific antibodies. In FAB assays, blocking antibodies initiated upon AIT were shown to prevent formation of Bet v 1-IgE complexes of an indicator serum pool and significantly correlated with clinical readout. Inhibition mediator release assays using patient-specific IgE for passive sensitization revealed therapy-induced blocking capacities with very good correlation to NPT results. Notably, this assay was the only one to detect a non-responder during treatment in this pilot study.

Conclusions

Clinical outcome of AIT depends on induction of blocking antibodies able to prevent the patient’s own IgE from allergen binding. Monitoring of clinical efficacy seems to be best achieved using the inhibition mediator release assay, as development of relevant blocking antibodies can be verified in a patient-tailored manner.
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Literature
3.
go back to reference Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M, Nelson H, Akdis CA. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131(1288–1296):e1283. Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M, Nelson H, Akdis CA. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131(1288–1296):e1283.
4.
go back to reference Plattsmills TAE, Maur RKV, Ishizaka K, Norman PS, Lichtenstein LM. Iga and Igg anti-ragweed antibodies in nasal secretions—quantitative measurements of antibodies and correlation with inhibition of histamine-release. J Clin Investig. 1976;57:1041–50.CrossRef Plattsmills TAE, Maur RKV, Ishizaka K, Norman PS, Lichtenstein LM. Iga and Igg anti-ragweed antibodies in nasal secretions—quantitative measurements of antibodies and correlation with inhibition of histamine-release. J Clin Investig. 1976;57:1041–50.CrossRef
5.
go back to reference James LK, Shamji MH, Walker SM, Wilson DR, Wachholz PA, Francis JN, Jacobson MR, Kimber I, Till SJ, Durham SR. Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies. J Allergy Clin Immunol. 2011;127:509–16.CrossRefPubMed James LK, Shamji MH, Walker SM, Wilson DR, Wachholz PA, Francis JN, Jacobson MR, Kimber I, Till SJ, Durham SR. Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies. J Allergy Clin Immunol. 2011;127:509–16.CrossRefPubMed
6.
go back to reference Vizzardelli C, Gindl M, Roos S, Mobs C, Nagl B, Zimmann F, Sexl V, Kenner L, Neunkirchner A, Zlabinger GJ, et al. Blocking antibodies induced by allergen-specific immunotherapy ameliorate allergic airway disease in a human/mouse chimeric model. Allergy. 2018;73:851–61.CrossRefPubMed Vizzardelli C, Gindl M, Roos S, Mobs C, Nagl B, Zimmann F, Sexl V, Kenner L, Neunkirchner A, Zlabinger GJ, et al. Blocking antibodies induced by allergen-specific immunotherapy ameliorate allergic airway disease in a human/mouse chimeric model. Allergy. 2018;73:851–61.CrossRefPubMed
7.
go back to reference Groh N, von Loetzen CS, Subbarayal B, Mobs C, Vogel L, Hoffmann A, Fotisch K, Koutsouridou A, Randow S, Volker E, et al. IgE and allergen-specific immunotherapy-induced IgG(4) recognize similar epitopes of Bet v 1, the major allergen of birch pollen. Clin Exp Allergy. 2017;47:693–703.CrossRefPubMed Groh N, von Loetzen CS, Subbarayal B, Mobs C, Vogel L, Hoffmann A, Fotisch K, Koutsouridou A, Randow S, Volker E, et al. IgE and allergen-specific immunotherapy-induced IgG(4) recognize similar epitopes of Bet v 1, the major allergen of birch pollen. Clin Exp Allergy. 2017;47:693–703.CrossRefPubMed
8.
go back to reference Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014;133:621–31.CrossRefPubMed Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014;133:621–31.CrossRefPubMed
9.
go back to reference Shamji MH, Kappen JH, Akdis M, Jensen-Jarolim E, Knol EF, Kleine-Tebbe J, Bohle B, Chaker AM, Till SJ, Valenta R, et al. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper. Allergy. 2017;72:1156–73.CrossRefPubMed Shamji MH, Kappen JH, Akdis M, Jensen-Jarolim E, Knol EF, Kleine-Tebbe J, Bohle B, Chaker AM, Till SJ, Valenta R, et al. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper. Allergy. 2017;72:1156–73.CrossRefPubMed
10.
go back to reference Wachholz PA, Durham SR. Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol. 2004;4:313–8.CrossRefPubMed Wachholz PA, Durham SR. Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol. 2004;4:313–8.CrossRefPubMed
11.
go back to reference Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol. 2011;127:18–27.CrossRefPubMed Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol. 2011;127:18–27.CrossRefPubMed
12.
go back to reference Di Lorenzo G, Mansueto P, Pacor ML, Rizzo M, Castello F, Martinelli N, Ditta V, Lo Bianco C, Leto-Barone MS, D’Alcamo A, et al. Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy. J Allergy Clin Immunol. 2009;123:1103–10.CrossRefPubMed Di Lorenzo G, Mansueto P, Pacor ML, Rizzo M, Castello F, Martinelli N, Ditta V, Lo Bianco C, Leto-Barone MS, D’Alcamo A, et al. Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy. J Allergy Clin Immunol. 2009;123:1103–10.CrossRefPubMed
13.
go back to reference Gehlhar K, Schlaak M, Becker WM, Bufe A. Monitoring allergen immunotherapy of pollen-allergic patients: the ratio of allergen-specific IgG4 to IgG1 correlates with clinical outcome. Clin Exp Allergy. 1999;29:497–506.CrossRefPubMed Gehlhar K, Schlaak M, Becker WM, Bufe A. Monitoring allergen immunotherapy of pollen-allergic patients: the ratio of allergen-specific IgG4 to IgG1 correlates with clinical outcome. Clin Exp Allergy. 1999;29:497–506.CrossRefPubMed
14.
go back to reference Lima MT, Wilson D, Pitkin L, Roberts A, Nouri-Aria K, Jacobson M, Walker S, Durham S. Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial. Clin Exp Allergy. 2002;32:507–14.CrossRefPubMed Lima MT, Wilson D, Pitkin L, Roberts A, Nouri-Aria K, Jacobson M, Walker S, Durham S. Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial. Clin Exp Allergy. 2002;32:507–14.CrossRefPubMed
15.
go back to reference Eifan AO, Akkoc T, Yildiz A, Keles S, Ozdemir C, Bahceciler NN, Barlan IB. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy. 2010;40:922–32.CrossRefPubMed Eifan AO, Akkoc T, Yildiz A, Keles S, Ozdemir C, Bahceciler NN, Barlan IB. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy. 2010;40:922–32.CrossRefPubMed
17.
go back to reference Rolinck-Werninghaus C, Kopp M, Liebke C, Lange J, Wahn U, Niggemann B. Lack of detectable alterations in immune responses during sublingual immunotherapy in children with seasonal allergic rhinoconjunctivitis to grass pollen. Int Arch Allergy Immunol. 2005;136:134–41.CrossRefPubMed Rolinck-Werninghaus C, Kopp M, Liebke C, Lange J, Wahn U, Niggemann B. Lack of detectable alterations in immune responses during sublingual immunotherapy in children with seasonal allergic rhinoconjunctivitis to grass pollen. Int Arch Allergy Immunol. 2005;136:134–41.CrossRefPubMed
18.
go back to reference Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, Till SJ. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol. 2008;121:1120–5.CrossRefPubMed Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, Till SJ. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol. 2008;121:1120–5.CrossRefPubMed
19.
go back to reference Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol. 2003;33:1205–14.CrossRefPubMed Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol. 2003;33:1205–14.CrossRefPubMed
20.
go back to reference Pilette C, Nouri-Aria KT, Jacobson MR, Wilcock LK, Detry B, Walker SM, Francis JN, Durham SR. Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. J Immunol. 2007;178:4658–66.CrossRefPubMed Pilette C, Nouri-Aria KT, Jacobson MR, Wilcock LK, Detry B, Walker SM, Francis JN, Durham SR. Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. J Immunol. 2007;178:4658–66.CrossRefPubMed
21.
go back to reference Mobs C, Slotosch C, Loffler H, Jakob T, Hertl M, Pfutzner W. Birch pollen immunotherapy leads to differential induction of regulatory T cells and delayed helper T cell immune deviation. J Immunol. 2010;184:2194–203.CrossRefPubMed Mobs C, Slotosch C, Loffler H, Jakob T, Hertl M, Pfutzner W. Birch pollen immunotherapy leads to differential induction of regulatory T cells and delayed helper T cell immune deviation. J Immunol. 2010;184:2194–203.CrossRefPubMed
22.
go back to reference Gadermaier E, Staikuniene J, Scheiblhofer S, Thalhamer J, Kundi M, Westritschnig K, Swoboda I, Flicker S, Valenta R. Recombinant allergen-based monitoring of antibody responses during injection grass pollen immunotherapy and after 5 years of discontinuation. Allergy. 2011;66:1174–82.CrossRefPubMed Gadermaier E, Staikuniene J, Scheiblhofer S, Thalhamer J, Kundi M, Westritschnig K, Swoboda I, Flicker S, Valenta R. Recombinant allergen-based monitoring of antibody responses during injection grass pollen immunotherapy and after 5 years of discontinuation. Allergy. 2011;66:1174–82.CrossRefPubMed
23.
go back to reference Subbarayal B, Schiller D, Mobs C, de Jong NW, Ebner C, Reider N, Bartel D, Lidholm J, Pfutzner W, van Wijk RG, et al. Kinetics, cross-reactivity, and specificity of Bet v 1-specific IgG4 antibodies induced by immunotherapy with birch pollen. Allergy. 2013;68:1377–86.CrossRefPubMed Subbarayal B, Schiller D, Mobs C, de Jong NW, Ebner C, Reider N, Bartel D, Lidholm J, Pfutzner W, van Wijk RG, et al. Kinetics, cross-reactivity, and specificity of Bet v 1-specific IgG4 antibodies induced by immunotherapy with birch pollen. Allergy. 2013;68:1377–86.CrossRefPubMed
24.
go back to reference Hoh RA, Joshi SA, Liu Y, Wang C, Roskin KM, Lee JY, Pham T, Looney TJ, Jackson KJL, Dixit VP, et al. Single B-cell deconvolution of peanut-specific antibody responses in allergic patients. J Allergy Clin Immunol. 2016;137:157–67.CrossRefPubMed Hoh RA, Joshi SA, Liu Y, Wang C, Roskin KM, Lee JY, Pham T, Looney TJ, Jackson KJL, Dixit VP, et al. Single B-cell deconvolution of peanut-specific antibody responses in allergic patients. J Allergy Clin Immunol. 2016;137:157–67.CrossRefPubMed
25.
go back to reference Jakobsen CG, Bodtger U, Poulsen LK, Roggen EL. Vaccination for birch pollen allergy: comparison of the affinities of specific immunoglobulins E, G1 and G4 measured by surface plasmon resonance. Clin Exp Allergy. 2005;35:193–8.CrossRefPubMed Jakobsen CG, Bodtger U, Poulsen LK, Roggen EL. Vaccination for birch pollen allergy: comparison of the affinities of specific immunoglobulins E, G1 and G4 measured by surface plasmon resonance. Clin Exp Allergy. 2005;35:193–8.CrossRefPubMed
26.
go back to reference Wang J, Lin J, Bardina L, Goldis M, Nowak-Wegrzyn A, Shreffler WG, Sampson HA. Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol. 2010;125:695–702.CrossRefPubMedPubMedCentral Wang J, Lin J, Bardina L, Goldis M, Nowak-Wegrzyn A, Shreffler WG, Sampson HA. Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol. 2010;125:695–702.CrossRefPubMedPubMedCentral
27.
go back to reference Wolf M, Twaroch TE, Huber S, Reithofer M, Steiner M, Aglas L, Hauser M, Aloisi I, Asam C, Hofer H, et al. Amb a 1 isoforms: unequal siblings with distinct immunological features. Allergy. 2017;72:1874–82.CrossRefPubMedPubMedCentral Wolf M, Twaroch TE, Huber S, Reithofer M, Steiner M, Aglas L, Hauser M, Aloisi I, Asam C, Hofer H, et al. Amb a 1 isoforms: unequal siblings with distinct immunological features. Allergy. 2017;72:1874–82.CrossRefPubMedPubMedCentral
28.
go back to reference Gieras A, Cejka P, Blatt K, Focke-Tejkl M, Linhart B, Flicker S, Stoecklinger A, Marth K, Drescher A, Thalhamer J, et al. Mapping of conformational IgE epitopes with peptide-specific monoclonal antibodies reveals simultaneous binding of different IgE antibodies to a surface patch on the major birch pollen allergen, Bet v 1. J Immunol. 2011;186:5333–44.CrossRefPubMed Gieras A, Cejka P, Blatt K, Focke-Tejkl M, Linhart B, Flicker S, Stoecklinger A, Marth K, Drescher A, Thalhamer J, et al. Mapping of conformational IgE epitopes with peptide-specific monoclonal antibodies reveals simultaneous binding of different IgE antibodies to a surface patch on the major birch pollen allergen, Bet v 1. J Immunol. 2011;186:5333–44.CrossRefPubMed
29.
go back to reference Jarolim E, Rumpold H, Endler AT, Ebner H, Breitenbach M, Scheiner O, Kraft D. Ige and Igg antibodies of patients with allergy to birch pollen as tools to define the allergen profile of Betula verrucosa. Allergy. 1989;44:385–95.CrossRefPubMed Jarolim E, Rumpold H, Endler AT, Ebner H, Breitenbach M, Scheiner O, Kraft D. Ige and Igg antibodies of patients with allergy to birch pollen as tools to define the allergen profile of Betula verrucosa. Allergy. 1989;44:385–95.CrossRefPubMed
30.
go back to reference Didier A, Melac M, Montagut A, Lheritier-Barrand M, Tabar A, Worm M. Agreement of efficacy assessments for five-grass pollen sublingual tablet immunotherapy. Allergy. 2009;64:166–71.CrossRefPubMed Didier A, Melac M, Montagut A, Lheritier-Barrand M, Tabar A, Worm M. Agreement of efficacy assessments for five-grass pollen sublingual tablet immunotherapy. Allergy. 2009;64:166–71.CrossRefPubMed
31.
go back to reference Wallner M, Hauser M, Himly M, Zaborsky N, Mutschlechner S, Harrer A, Asam C, Pichler U, van Ree R, Briza P, et al. Reshaping the Bet v 1 fold modulates T–H polarization. J Allergy Clin Immunol. 2011;127:1571–8.CrossRefPubMedPubMedCentral Wallner M, Hauser M, Himly M, Zaborsky N, Mutschlechner S, Harrer A, Asam C, Pichler U, van Ree R, Briza P, et al. Reshaping the Bet v 1 fold modulates T–H polarization. J Allergy Clin Immunol. 2011;127:1571–8.CrossRefPubMedPubMedCentral
32.
go back to reference Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998;102:558–62.CrossRefPubMed Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998;102:558–62.CrossRefPubMed
33.
go back to reference Shamji MH, Wilcock LK, Wachholz PA, Dearman RJ, Kimber I, Wurtzen PA, Larche M, Durham SR, Francis JN. The IgE-facilitated allergen binding (FAB) assay: validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses. J Immunol Methods. 2006;317:71–9.CrossRefPubMedPubMedCentral Shamji MH, Wilcock LK, Wachholz PA, Dearman RJ, Kimber I, Wurtzen PA, Larche M, Durham SR, Francis JN. The IgE-facilitated allergen binding (FAB) assay: validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses. J Immunol Methods. 2006;317:71–9.CrossRefPubMedPubMedCentral
34.
go back to reference Vogel L, Luttkopf D, Hatahet L, Haustein D, Vieths S. Development of a functional in vitro assay as a novel tool for the standardization of allergen extracts in the human system. Allergy. 2005;60:1021–8.CrossRefPubMed Vogel L, Luttkopf D, Hatahet L, Haustein D, Vieths S. Development of a functional in vitro assay as a novel tool for the standardization of allergen extracts in the human system. Allergy. 2005;60:1021–8.CrossRefPubMed
35.
go back to reference Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, Valenta R, Niederberger V. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol. 2005;116:347–54.CrossRefPubMed Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, Valenta R, Niederberger V. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol. 2005;116:347–54.CrossRefPubMed
36.
go back to reference Shamji MH, Durham SR. Mechanisms of immunotherapy to aeroallergens. Clin Exp Allergy. 2011;41:1235–46.CrossRefPubMed Shamji MH, Durham SR. Mechanisms of immunotherapy to aeroallergens. Clin Exp Allergy. 2011;41:1235–46.CrossRefPubMed
37.
go back to reference Shamji MH, Ljorring C, Francis JN, Calderon M, Larche M, Kimber I, Frew AJ, Ipsen H, Lund K, Wurtzen PA, Durham SR. Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy. 2012;67:217–26.CrossRefPubMed Shamji MH, Ljorring C, Francis JN, Calderon M, Larche M, Kimber I, Frew AJ, Ipsen H, Lund K, Wurtzen PA, Durham SR. Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy. 2012;67:217–26.CrossRefPubMed
38.
go back to reference Shamji MH, Layhadi JA, Scadding GW, Cheung DK, Calderon MA, Turka LA, Phippard D, Durham SR. Basophil expression of diamine oxidase: a novel biomarker of allergen immunotherapy response. J Allergy Clin Immunol. 2015;135(913–921):e919. Shamji MH, Layhadi JA, Scadding GW, Cheung DK, Calderon MA, Turka LA, Phippard D, Durham SR. Basophil expression of diamine oxidase: a novel biomarker of allergen immunotherapy response. J Allergy Clin Immunol. 2015;135(913–921):e919.
39.
go back to reference Lalek N, Kosnik M, Silar M, Korosec P. Immunoglobulin G-dependent changes in basophil allergen threshold sensitivity during birch pollen immunotherapy. Clin Exp Allergy. 2010;40:1186–93.CrossRefPubMed Lalek N, Kosnik M, Silar M, Korosec P. Immunoglobulin G-dependent changes in basophil allergen threshold sensitivity during birch pollen immunotherapy. Clin Exp Allergy. 2010;40:1186–93.CrossRefPubMed
40.
go back to reference Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, Gerth van Wijk R, Halken S, Larenas-Linnemann D, Pawankar R, Pitsios C, et al. EAACI guidelines on allergen immunotherapy: allergic rhinoconjunctivitis. Allergy. 2018;73:765–98.CrossRefPubMed Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, Gerth van Wijk R, Halken S, Larenas-Linnemann D, Pawankar R, Pitsios C, et al. EAACI guidelines on allergen immunotherapy: allergic rhinoconjunctivitis. Allergy. 2018;73:765–98.CrossRefPubMed
Metadata
Title
Does clinical outcome of birch pollen immunotherapy relate to induction of blocking antibodies preventing IgE from allergen binding? A pilot study monitoring responses during first year of AIT
Authors
Sara Huber
Roland Lang
Markus Steiner
Lorenz Aglas
Fatima Ferreira
Michael Wallner
Thomas Hawranek
Gabriele Gadermaier
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Clinical and Translational Allergy / Issue 1/2018
Electronic ISSN: 2045-7022
DOI
https://doi.org/10.1186/s13601-018-0226-7

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