Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper.
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.


METHODS
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.
Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.|MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Allergy and Clinical Immunology, Immunomodulation and Tolerance Group, Imperial College London, London, UK.
M H
http://orcid.org/0000-0003-3425-3463
MH
Shamji
Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.|MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Allergy and Clinical Immunology, Immunomodulation and Tolerance Group, Imperial College London, London, UK.|Department of Pulmonology, STZ Centre of Excellence for Asthma & COPD, Sint Franciscus Vlietland Group, Rotterdam, The Netherlands.
J H
JH
Kappen
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
M
M
Akdis
Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria.|The interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, Vienna, Austria.
E
http://orcid.org/0000-0003-4019-5765
E
Jensen-Jarolim
Departments Immunology and Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
E F
EF
Knol
Allergy & Asthma Center Westend, Outpatient Clinic and Research Center Hanf, Ackermann & Kleine-Tebbe, Berlin, Germany.
J
J
Kleine-Tebbe
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
B
B
Bohle
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center Munich, Munich, Germany.|Department of Otolaryngology, Allergy Section, Klinikum rechts der Isar, Technische Universität, Munich, Germany.
A M
AM
Chaker
Division of Asthma, Allergy and Lung Biology, King's College London, London, UK.|Department of Allergy, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
S J
SJ
Till
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
R
R
Valenta
Allergy Clinic, Copenhagen University Hospital at Gentofte, Copenhagen, Denmark.
L K
LK
Poulsen
Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.|MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Allergy and Clinical Immunology, Immunomodulation and Tolerance Group, Imperial College London, London, UK.
M A
MA
Calderon
Division of Allergy, Department of Pulmonology, Arnaud de Villeneuve Hospital, University Hospital of Montpellier and Sorbonne University, Paris, France.
P
P
Demoly
Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Center for Rhinology and Allergology, Wiesbaden, Germany.
O
http://orcid.org/0000-0003-4374-9639
O
Pfaar
Allergy Learning and Consulting, Copenhagen, Denmark.
L
L
Jacobsen
Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.|MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Allergy and Clinical Immunology, Immunomodulation and Tolerance Group, Imperial College London, London, UK.
S R
SR
Durham
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center Munich, Munich, Germany.
C B
CB
Schmidt-Weber
D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D003233:Conjunctivitis, Allergic / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D065631:Rhinitis, Allergic / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome
D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E
IgE-FAB; IgG4; allergen immunotherapy; basophil activation; biomarkers