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

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.

Fig. 1

The principle of the BAT/HistaFlow