Molecular diagnosis for allergen immunotherapy

Abstract

The extensive use of allergen molecules in birth cohort studies revealed that atopic sensitization is a sequential IgE response to distinct non-cross-reacting molecules from the same allergenic source (ie, molecular spreading), starting with an initiator molecule. This phenomenon reaches different degrees of progression (monomolecular, oligomolecular, and polymolecular) according to the individual atopic propensity and allergen exposure, thus producing an extreme heterogeneity of IgE sensitization profiles in patient populations. In patients with allergic rhinitis, the broader the IgE molecular sensitization profile, the greater is the risk of asthma and other allergic comorbidities, such as oral allergy syndrome. Hence it has been proposed to anticipate immunologic intervention at disease onset (early allergen immunotherapy) or even earlier during the preclinical sensitization stage (allergen immunoprophylaxis). Diagnostic algorithms based on singleplex or multiplex molecular IgE tests allow the discrimination of genuine from cross-reacting sensitization and the selection of the right extracts for allergen immunotherapy composition. Patients with extreme molecular poly-sensitization and greater risk of asthma or other IgE-mediated comorbidities, can be easily identified by means of allergen microarray or macroarray procedures and might benefit from anti-IgE treatment. IgE molecular tests have opened the era of precision allergology, and their routine use should aim at cost-effectiveness, according to the principles of the Choosing Wisely initiative.

The Role of Der p 23 Sensitization: An Analysis of 474 Patients Sensitized to Mite

“…could not identify the majority of patients from southern Germany without sensitization to the 2 major allergens Der p 1 and/or Der p 2 and, therefore, is not suitable to close a diagnostic gap that arises when exclusively testing with components. On the other hand, specific knowledge of the exact sensitization profile is indispensable for the decision for allergen immunotherapy and its probable success [25,26]. Furthermore, Jiménez-Feijoo et al [10] reported that all elven HDM allergic patients of their collective who did not respond to immunotherapy were sensitized towards Der p 23.…”

A WAO — ARIA — GA2LEN consensus document on molecular-based allergy diagnosis (PAMD@): Update 2020

“…[310][311][312] These algorithms all incorporate the idea that detecting sensitization to genuine components is essential. 313 Although AIT for pollen-associated food allergy has shown beneficial effects in some studies, particularly for oral symptoms, other clinical trials have not shown similar outcomes; thus AIT cannot be recommended as a treatment in these cases and should be considered only when respiratory symptoms are present. [314][315][316][317][318] However, there are some fascinating potential applications in the field of immunotherapy: a research group in Vienna has recently generated mimotopes using a monoclonal antibody (BIP3) recognizing highmolecular-weight glycoproteins in birch and mugwort pollens, celery, and Apiaceae spices (anise, fennel, coriander, and cumin), which are responsible for the "celery-mugwort-birch-spice syndrome".…”

Allergen Immunotherapy in Children User’s Guide

“…Following adequate diagnosis algorithms, and a combination of in vivo and in vitro methods—which may include molecular allergology tools—are mandatory for deciding AIT intervention strategy in pediatric‐allergic patients . A comprehensive clinical guide for allergy diagnosis has already been published .…”