M H Shamji1,2,3, J H Kappen1,2,3,4, M Akdis5, E Jensen-Jarolim6,7, E F Knol8, J Kleine-Tebbe9, B Bohle10, A M Chaker11,12, S J Till13,14, R Valenta15, L K Poulsen16, M A Calderon1,2,3, P Demoly17, O Pfaar18,19, L Jacobsen20, S R Durham1,2,3, C B Schmidt-Weber11. 1. Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK. 2. MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK. 3. Allergy and Clinical Immunology, Immunomodulation and Tolerance Group, Imperial College London, London, UK. 4. Department of Pulmonology, STZ Centre of Excellence for Asthma & COPD, Sint Franciscus Vlietland Group, Rotterdam, The Netherlands. 5. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland. 6. Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria. 7. The interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, Vienna, Austria. 8. Departments Immunology and Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands. 9. Allergy & Asthma Center Westend, Outpatient Clinic and Research Center Hanf, Ackermann & Kleine-Tebbe, Berlin, Germany. 10. Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria. 11. Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center Munich, Munich, Germany. 12. Department of Otolaryngology, Allergy Section, Klinikum rechts der Isar, Technische Universität, Munich, Germany. 13. Division of Asthma, Allergy and Lung Biology, King's College London, London, UK. 14. Department of Allergy, Guy's and St. Thomas' NHS Foundation Trust, London, UK. 15. Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. 16. Allergy Clinic, Copenhagen University Hospital at Gentofte, Copenhagen, Denmark. 17. Division of Allergy, Department of Pulmonology, Arnaud de Villeneuve Hospital, University Hospital of Montpellier and Sorbonne University, Paris, France. 18. Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 19. Center for Rhinology and Allergology, Wiesbaden, Germany. 20. Allergy Learning and Consulting, Copenhagen, Denmark.
Abstract
BACKGROUND: Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. METHOD: The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). RESULTS: All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. CONCLUSIONS: It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.
BACKGROUND: Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. METHOD: The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). RESULTS: All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. CONCLUSIONS: It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.
Authors: Amedee Renand; Mohamed H Shamji; Kristina M Harris; Tielin Qin; Erik Wambre; Guy W Scadding; Peter A Wurtzen; Stephen J Till; Alkis Togias; Gerald T Nepom; William W Kwok; Stephen R Durham Journal: J Allergy Clin Immunol Date: 2017-11-09 Impact factor: 10.793
Authors: Sarah K Wise; Sandra Y Lin; Elina Toskala; Richard R Orlandi; Cezmi A Akdis; Jeremiah A Alt; Antoine Azar; Fuad M Baroody; Claus Bachert; G Walter Canonica; Thomas Chacko; Cemal Cingi; Giorgio Ciprandi; Jacquelynne Corey; Linda S Cox; Peter Socrates Creticos; Adnan Custovic; Cecelia Damask; Adam DeConde; John M DelGaudio; Charles S Ebert; Jean Anderson Eloy; Carrie E Flanagan; Wytske J Fokkens; Christine Franzese; Jan Gosepath; Ashleigh Halderman; Robert G Hamilton; Hans Jürgen Hoffman; Jens M Hohlfeld; Steven M Houser; Peter H Hwang; Cristoforo Incorvaia; Deborah Jarvis; Ayesha N Khalid; Maritta Kilpeläinen; Todd T Kingdom; Helene Krouse; Desiree Larenas-Linnemann; Adrienne M Laury; Stella E Lee; Joshua M Levy; Amber U Luong; Bradley F Marple; Edward D McCoul; K Christopher McMains; Erik Melén; James W Mims; Gianna Moscato; Joaquim Mullol; Harold S Nelson; Monica Patadia; Ruby Pawankar; Oliver Pfaar; Michael P Platt; William Reisacher; Carmen Rondón; Luke Rudmik; Matthew Ryan; Joaquin Sastre; Rodney J Schlosser; Russell A Settipane; Hemant P Sharma; Aziz Sheikh; Timothy L Smith; Pongsakorn Tantilipikorn; Jody R Tversky; Maria C Veling; De Yun Wang; Marit Westman; Magnus Wickman; Mark Zacharek Journal: Int Forum Allergy Rhinol Date: 2018-02 Impact factor: 3.858
Authors: Carmen Rondón; Ibon Eguíluz-Gracia; Mohamed H Shamji; Janice A Layhadi; María Salas; María José Torres; Paloma Campo Journal: Curr Allergy Asthma Rep Date: 2018-10-13 Impact factor: 4.806