IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper

Ignacio J Ansotegui; Giovanni Melioli; Giorgio Walter Canonica; Luis Caraballo; Elisa Villa; Motohiro Ebisawa; Giovanni Passalacqua; Eleonora Savi; Didier Ebo; R Maximiliano Gómez; Olga Luengo Sánchez; John J Oppenheimer; Erika Jensen-Jarolim; David A Fischer; Tari Haahtela; Martti Antila; Jean J Bousquet; Victoria Cardona; Wen Chin Chiang; Pascal M Demoly; Lawrence M DuBuske; Marta Ferrer Puga; Roy Gerth van Wijk; Sandra Nora González Díaz; Alexei Gonzalez-Estrada; Edgardo Jares; Ayse Füsun Kalpaklioğlu; Luciana Kase Tanno; Marek L Kowalski; Dennis K Ledford; Olga Patricia Monge Ortega; Mário Morais Almeida; Oliver Pfaar; Lars K Poulsen; Ruby Pawankar; Harald E Renz; Antonino G Romano; Nelson A Rosário Filho; Lanny Rosenwasser; Mario A Sánchez Borges; Enrico Scala; Gian-Enrico Senna; Juan Carlos Sisul; Mimi L K Tang; Bernard Yu-Hor Thong; Rudolf Valenta; Robert A Wood; Torsten Zuberbier

doi:10.1016/j.waojou.2019.100080

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper

World Allergy Organ J. 2020 Feb 25;13(2):100080. doi: 10.1016/j.waojou.2019.100080. eCollection 2020 Feb.

Authors

Ignacio J Ansotegui¹, Giovanni Melioli², Giorgio Walter Canonica³, Luis Caraballo⁴, Elisa Villa⁵, Motohiro Ebisawa⁶, Giovanni Passalacqua⁷, Eleonora Savi⁸, Didier Ebo⁹, R Maximiliano Gómez¹⁰, Olga Luengo Sánchez¹¹, John J Oppenheimer¹², Erika Jensen-Jarolim¹³, David A Fischer¹⁴, Tari Haahtela¹⁵, Martti Antila¹⁶, Jean J Bousquet^{17

18

19

20

21}, Victoria Cardona²², Wen Chin Chiang²³, Pascal M Demoly^{24

25}, Lawrence M DuBuske²⁶, Marta Ferrer Puga²⁷, Roy Gerth van Wijk²⁸, Sandra Nora González Díaz²⁹, Alexei Gonzalez-Estrada³⁰, Edgardo Jares³¹, Ayse Füsun Kalpaklioğlu³², Luciana Kase Tanno³³, Marek L Kowalski³⁴, Dennis K Ledford³⁵, Olga Patricia Monge Ortega³⁶, Mário Morais Almeida³⁷, Oliver Pfaar³⁸, Lars K Poulsen³⁹, Ruby Pawankar⁴⁰, Harald E Renz⁴¹, Antonino G Romano⁴², Nelson A Rosário Filho⁴³, Lanny Rosenwasser⁴⁴, Mario A Sánchez Borges⁴⁵, Enrico Scala⁴⁶, Gian-Enrico Senna⁴⁷, Juan Carlos Sisul⁴⁸, Mimi L K Tang⁴⁹, Bernard Yu-Hor Thong⁵⁰, Rudolf Valenta^{51

52

53}, Robert A Wood⁵⁴, Torsten Zuberbier⁵⁵

Affiliations

¹ Hospital Quironsalud Bizkaia, Bilbao-Erandio, Spain.
² Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
³ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Personalized Medicine, Asthma and Allergy, Humanitas Research Hospital, Rozzano, Milan, Italy.
⁴ Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.
⁵ Azienda Sanitaria Locale di Vercelli, S.C. Pneumologia, Vercelli, Italia.
⁶ Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan.
⁷ Allergy and Respiratory Diseases, IRCCS Policlinico San Martino, University of Genoa, Genoa, Italy.
⁸ Ospedale Civile, Gossolengo, PC, Italy.
⁹ Department of Immunology - Allergology - Rheumatology, Antwerp University Hospital, Antwerp University, Department Immunology and Allergology, AZ Jan Palfijn Gent, Ghent, Belgium.
¹⁰ Universidad Católica de Salta, Fundación Ayre, Buenos Aires, Argentina.
¹¹ Allergy Section, Department of Internal Medicine, Vall d'Hebron University Hospital, Barcelona, Spain.
¹² Pulmonary & Allergy Associates, Denville, NJ, USA.
¹³ Institute for Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, The Interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, Vienna, Austria.
¹⁴ Fischer Medicine Professional Corporation, Barrie, Ontario, Canada.
¹⁵ Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland.
¹⁶ Clínica de Alergía, Sorocaba, São Paulo, Brazil.
¹⁷ MACVIA-France, Montpellier, France.
¹⁸ INSERM, Villejuif, France.
¹⁹ Université Versailles St-Quentin-en-Yvelines, Montigny le Bretonneux, France.
²⁰ Euforea, Brussels, Belgium.
²¹ CHU Montpellier, France.
²² Universitat Autónoma de Barcelona, Hospital Universitario Vall d'Hebron, Servicio de Medicina Interna, Sección de Alergología, Barcelona, Spain.
²³ Mount Elizabeth Medical Centre, Chiang Children's Allergy & Asthma Clinic, Singapore, Singapore.
²⁴ University Hospital Montpellier, Montpellier, France.
²⁵ Sorbonne Université, Paris, France.
²⁶ Immunology Research Institute of New England, Gardner, MA, USA.
²⁷ The Unidad de Educación Médica, Department of Medical Education, School of Medicine, Clinica Universitad de Navarra, Navarra, Spain.
²⁸ Erasmus MC, Sector Allergologie, Rotterdam, the Netherlands.
²⁹ Universidad Autónoma de Nuevo León, Hospital Universitario, Monterrey, Nuevo León, Mexico.
³⁰ Department of Allergy, Mayo Clinic, Jacksonville, FL, USA.
³¹ Femeca Femedica, Buenos Aires, Argentina.
³² Kirikkale Universitesi, Tip Fakultesi, Kirikkale, Turkey.
³³ Hospital Sírio Libanês, University of São Paulo, São Paulo, Brazil.
³⁴ Faculty of Medicine, Department of Clinical Immunology & Allergy, Medical University of Łódź, Łódź, Poland.
³⁵ University of South Florida College of Medicine, Tampa, FL, USA.
³⁶ Allergology Unit, San Juan de Dios Hospital, University of Costa Rica, San José, Costa Rica.
³⁷ Hospital CUF-Descobertas, Lisbon, Portugal.
³⁸ Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany.
³⁹ Gentofte University Hospital, Lab for Allergology, Allergy Clinic, Hellerup, Denmark.
⁴⁰ Nippon Medical School, Dept. of Otolaryngology, Tokyo, Japan.
⁴¹ University Hospital GI & MR GmbH, Institute of Laboratory Medicine & Pathology, Standort Marburg, Marburg, Germany.
⁴² Stallergenes, Rome, Italy.
⁴³ University of Parana, Curitiba, PR, Brazil.
⁴⁴ University of Missouri at Kansas City, School of Medicine, Kansas City, MO, USA.
⁴⁵ Centro Médico Docente La Trinidad, Caracas, Venezuela.
⁴⁶ Experimental Allergy Unit, Istituto Dermopatico dell'Immacolata, Rome, Italy.
⁴⁷ Ospedale Civile Maggiore, Verona, Italy.
⁴⁸ Allergy & Asthma Institute, Asunción, Paraguay.
⁴⁹ Royal Children's Hospital, Department of Allergy & Immunology, Parkville, Victoria, Australia.
⁵⁰ Tan Tock Seng Hospital, Deptartment of Rheumatology, Allergy & Immunology, Singapore, Singapore.
⁵¹ Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
⁵² NRC Institute of Immunology FMBA of Russia, Moscow, Russia.
⁵³ Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russia.
⁵⁴ Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.
⁵⁵ Campus Charite Mitte, Klinik fur Dermatologie & Allergologie, Berlin, Germany.

Abstract

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.

Keywords: AAAAI, American Academy of Allergy Asthma and Immunology; ABA, Allergen Bead Array; ACAAI, American College of Allergy Asthma and Immunology; AEC, Allergen Exposure Chambers; AIT, allergen immunotherapy; AP, Alkaline Phosphatase; AU/mL, Allergenic Units milliLiter; Allergy; Anti-IgE, Antibody against IgE; BAT, Basophil Activation Test; BAU/mL, Biologic Allergenic Units milliLiter; CBA, Cytometric Bead Array; CCD, Cross-reactive Carbohydrate Determinants; CDER, Center for Drug Evaluation and Research (USA); CL, Chemiluminescence; CaFE, Calibrated Fluorescence Enhancement; DBPCFC, Double-Blind Placebo-Controlled Food Challenge; Diagnostic strategies; EAACI, European Academy of Allergy and Immunology; EIA, Enzyme Immune Assay; ELISA, Enzyme Linked Immuno Sorbent Analysis; EMEA, European MEdicine Agencies; ENPP-3, EctoNucleotide Pyrophosphatase/Phosphodiesterase 3; FACS, Fluorescence-Activated Cell Sorting; FDA, Food and Drug Administration (U.S. Department of Health and Human Services); FEIA, Fluorescent Enzyme Immunoassays; FcεRI, High affinity IgE receptor; H1, Histamine 1 receptor; H2, Histamine 2 receptor; HPO, Horseradish Peroxidase; IDT, Intradermal Test; ISAC, Immuno-Solid phase Allergen Chip; IUIS, International Union of Immunological Societies; IVD, in vitro diagnostic tool; IgE; IgE, immunoglobulin E; In vitro tests; LAMP-3, Lysosomal-Associated Membrane Protein; MBAD, Molecule Based Allergy Diagnostics; MRGPRX2, Mas-related G protein receptor 2; NIH, National Institutes of Health (USA); NMBAs, NeuroMuscular Blocking Agents; NPA, Negative Percent Agreement; NSAIDs, Non-Steroidal Anti-Inflammatory Drugs; PPA, Positive Percent Agreement; PPT, Prick-Prick Test; RAST, Radio Allergo Sorbent Test; SCAR, severe cutaneous adverse drug reactions; SPT, Skin prick test; Skin tests; kUA/L, kilo Units of Allergen/Liter for allergen-specific IgE antibody assays; mAb, Monoclonal Antibody; pNPP, p-Nitrophenylphosphate; sIgE, specific IgE; w/v, weight /volume.