The allergenic activity and clinical impact of individual IgE-antibody binding molecules from indoor allergen sources

Abstract

A large number of allergens have been discovered but we know little about their potential to induce inflammation (allergenic activity) and symptoms. Nowadays, the clinical importance of allergens is determined by the frequency and intensity of their IgE antibody binding (allergenicity). This is a rather limited parameter considering the development of experimental allergology in the last 20 years and the criteria that support personalized medicine. Now it is known that some allergens, in addition to their IgE antibody binding properties, can induce inflammation through non IgE mediated pathways, which can increase their allergenic activity. There are several ways to evaluate the allergenic activity, among them the provocation tests, the demonstration of non-IgE mediated pathways of inflammation, case control studies of IgE-binding frequencies, and animal models of respiratory allergy. In this review we have explored the current status of basic and clinical research on allergenic activity of indoor allergens and confirm that, for most of them, this important property has not been investigated. However, during recent years important advances have been made in the field, and we conclude that for at least the following, allergenic activity has been demonstrated:

Are the Terms Major and Minor Allergens Useful for Precision Allergology?

“…It is known that there are allergens with high IgE-binding frequency but low clinical impact, and allergens with low IgE-binding frequency and high clinical impact for some patients (11)(12)(13)(14). Since CRD is a necessary step for future component resolved immunotherapy, it is crucial that the arrays include clinically relevant allergens, defined by several parameters in addition to IgE-binding (10).…”

“…In asthma, HDM allergens, cockroaches, molds, pet dander, and some pollens are risk factors, although, as expected, the relative importance of each of these sources depends on the geographic region. In this regard, two important advances have arisen; the use of component resolved diagnosis (CRD) and the characterization of the allergenic activity of several of those components ( 10 ).…”

“…A crucial step for understanding the clinical relevance of allergens is to differentiate their allergenicity (the property of inducing and binding IgE antibodies) from their allergenic activity, which means their capacity to induce inflammation, whatever the underlying mechanisms ( 7 , 10 ). The strength of the IgE response varies between individuals and between allergens (for example HDM vs. food allergens) and reflects the allergenicity; not always correlating with allergenic activity.…”

“…The strength of the IgE response varies between individuals and between allergens (for example HDM vs. food allergens) and reflects the allergenicity; not always correlating with allergenic activity. An update of the research on allergenic activity of indoor allergens was done recently, suggesting that, as occur with the characterization of the allergenic activity of extracts, a set of assays and criteria could help to determine the allergenic activity and clinical impact of IgE-binding molecules ( 10 ). Employing these assays, it seemed rational to accept that those IgE antibody binding components with positive in vivo provocation tests in humans (which might need GMP-grade batches of allergen), plus positive association in case-control studies and defined proinflammatory mechanisms of action, have a demonstrated allergenic activity, a property close to clinical relevance.…”

Mite Molecular Profile in the Th2-Polarized Moderate-to-Severe Persistent Asthma Endotype Subjected to High Allergen Exposure

“…Although former asthma reports – despite including only a limited number of HDM allergens – have generalized more elevated IgE responses to Der p 2 [60] and Der p 23 [61, 62] in the severe degree of the disease, our findings showed that only Der p 2 was significantly higher in the severe younger asthmatics, with higher – but not statistically significant – total IgE and sIgE to Der p 1, Der p 7, and Der p 21 titers, compared to moderate asthmatics. Elucidating how the majority (>75%) of both moderate and severe asthma patients recognize 4 or more HDM molecules can be intriguing; however, prior multivariate analyses have correlated the conjunction of different predisposing and/or protecting factors related to the environment – thus, natural exposure to mixtures of non-purified allergens and other elements influencing the effects of individual molecules – and the genetic background, to increasing pleomorphic mite-specific IgE responses [63, 64].…”