Precision medicine allergy immunoassay methods for assessing immunoglobulin E sensitization to aeroallergen molecules

Abstract

Molecular-based allergy diagnosis for the in vitro assessment of a patient immunoglobulin E (IgE) sensitization profile at the molecular level uses allergen molecules (also referred to as allergen components), which may be well-defined, highly purified, natural allergen components or recombinant allergens. Modern immunoassay methods used for the detection of specific IgE against aeroallergen components are either singleplex (such as the fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens, the enzyme-enhanced chemiluminescence immunoassay and the reversed enzyme allergosorbent test, with liquid-phase allergens), multiparameter (such as the line blot immunoassay for defined partial allergen diagnostics with allergen components coating membrane strips) or multiplex (such as the microarray-based immunoassay on immuno solid-phase allergen chip, and the two new multiplex nanotechnology-based immunoassays: the patient-friendly allergen nano-bead array, and the macroarray nanotechnology-based immunoassay used as a molecular allergy explorer). The precision medicine diagnostic work-up may be organized as an integrated “U-shape” approach, with a “top-down” approach (from symptoms to molecules) and a “bottom-up” approach (from molecules to clinical implications), as needed in selected patients. The comprehensive and accurate IgE sensitization molecular profiling, with identification of the relevant allergens, is indicated within the framework of a detailed patient’s clinical history to distinguish genuine IgE sensitization from sensitization due to cross-reactivity (especially in polysensitized patients), to assess unclear symptoms and unsatisfactory response to treatment, to reveal unexpected sensitizations, and to improve assessment of severity and risk aspects in some patients. Practical approaches, such as anamnesis molecular thinking, laboratory molecular thinking and postmolecular anamnesis, are sometimes applied. The component-resolved diagnosis of the specific IgE repertoire has a key impact on optimal decisions making for prophylactic and specific immunotherapeutic strategies tailored for the individual patient.

Keywords: Singleplex; Multiplex; Immunoglobulin E sensitization; Aeroallergens; Immunoassays

Core tip: Allergic respiratory diseases affect many people of all ages worldwide, showing increased prevalence, severity and complexity. New generation immunoassays using allergenic molecules represent a great precision medicine approach in research and clinical practice, allowing in vitro assessment of the immunoglobulin E (IgE) sensitization pattern at the molecular level, with favorable impact on allergy diagnosis and treatment, especially in selected patients with multiple aeroallergen sensitizations. The choice for a specific IgE immunoassay (singleplex, multiparameter or multiplex) for the allergenic extracts and molecular specificities, and the correct interpretation of the results, require optimal knowledge of the tests’ methodologies and characteristics, and good clinical judgments.