Molecular diagnosis for allergen immunotherapy (original) (raw)

Molecular Diagnosis of Allergy: The Pediatric Perspective

Frontiers in Pediatrics, 2019

In times of "Precision Medicine" it is fundamental to identify the individual disease phenotype in order to provide an individualized therapy for every patient. This concept is also becoming increasingly important for the treatment of allergic diseases. Thanks to the biological engineering of recombinant and native allergens for the assessment of allergen-specific IgE antibodies, it is now possible to easily obtain the individual sensitization profile of a patient. This allows the allergist to precisely identify the primary elicitor of an IgE response and, based on this knowledge, to choose the best treatment option. Several studies have observed the longitudinal evolution of sensitization profiles and identified a phenomenon termed "molecular spreading," which describes a broadening of the recognized allergen spectrum from a source over time. Additionally, the identification of marker proteins, which can trigger an IgE response or correlate with an increased risk for certain clinical symptoms, helps to establish an individual risk profile. This information may not only affect the decision-making concerning immunotherapy, but also opens up avenues for future investigations with regard to prevention strategies. We provide here an overview on the role of individual sensitization patterns and their predictive value.

Molecule-based diagnosis and allergen immunotherapy

European annals of allergy and clinical immunology, 2013

Allergen immunotherapy (AIT) represents the only way to modify the natural history of allergic diseases. Unfortunately, AIT is not always followed by a reduction in symptoms. The main reasons for such failure can be inadequate diagnosis and/or the poor treatment. In both cases, an incomplete or insufficient understanding of the component(s) responsible for the IgE sensitization on the one hand, and, on the other hand, the lack of a steady and reliable allergen mixture to be used for the desensitization process, could explain unsuccessful treatment. A more comprehensive IgE reactivity profile evaluation of the patient can be achieved by means of a molecule-based diagnostic approach, in order to distinguish genuine from panallergen-driven antigen recognition. At the same time, a better delineation of AIT products by means of molecular dissection, can allow a stronger correlation between diagnostic findings and immunotherapeutic intervention, thus facilitating the right prescription to...

Molecular aspects of allergens in atopic dermatitis

Current Opinion in Allergy & Clinical Immunology, 2017

Purpose of review Molecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens. Here we review recent work showing the usefulness of molecular allergology to study mechanisms of atopic dermatitis, for diagnosis and eventually for treatment and prevention of atopic dermatitis. Recent findings IgE sensitization to airborne, food-derived, microbial allergens, and autoallergens has been found to be associated with atopic dermatitis. Using defined allergen molecules and non-IgE-reactive allergen derivatives, evidence could be provided for the existence of IgE-and non-IgE-mediated mechanisms of inflammation in atopic dermatitis. Furthermore, effects of epicutaneous allergen administration on systemic allergen-specific immune responses have been studied. Multi-allergen tests containing micro-arrayed allergen molecules have been shown to be useful for the identification of culprit allergens in atopic dermatitis and may improve the management of atopic dermatitis by allergen-specific immunotherapy, allergen avoidance, and IgE-targeting therapies in a personalized medicine approach. Summary Molecular allergology allows for dissection of the pathomechanisms of atopic dermatitis, provides new forms of allergy diagnosis for identification of disease-causing allergens, and opens the door to new forms of management by allergen-specific and T cells-targeting or IgE-targeting interventions in a personalized medicine approach.

Interfaces between allergen structure and diagnosis: know your epitopes

Current allergy and asthma reports, 2015

Allergy diagnosis is based on the patient's clinical history and can be strengthened by tests that confirm the origin of sensitization. In the past 25 years, these tests have evolved from the exclusive in vivo or in vitro use of allergen extracts, to complementary molecular-based diagnostics that rely on in vitro measurements of IgE reactivity to individual allergens. For this to occur, an increase in our understanding of the molecular structure of allergens, largely due to the development of technologies such as molecular cloning and expression of recombinant allergens, X-ray crystallography, or nuclear magnetic resonance (NMR), has been essential. New in vitro microarray or multiplex systems are now available to measure IgE against a selected panel of purified natural or recombinant allergens. The determination of the three-dimensional structure of allergens has facilitated detailed molecular studies, including the analysis of antigenic determinants for diagnostic purposes.

Pre-treatment allergen-specific IgE analysis and outcomes of allergen immunotherapy

European Annals of Allergy and Clinical Immunology, 2021

Background. Patients show varied results to allergen immunotherapy (AIT). The reason for this variability is unclear. Objective. To describe the relationship between AIT efficacy and demographic characteristics, as well as pre-treatment plasma levels of specific IgE-antibodies to grass and birch pollen. Methods. A retrospective study was performed based on medical records of 128 patients who received AIT. The patients completed a questionnaire and pre-AIT plasma levels of allergen-specific IgE to grass and birch pollen were measured using EUROLINE DPA-Dx pollen 1 method. Results. Seventy percent of patients classified their allergic symptoms as less severe after AIT. Twenty-seven percent had received AIT targeting only grass pollen, 19% targeting only birch pollen, and 55% targeting both grass and birch. A total of 35 different IgE profiles were found across our study population. On comparison of the demographic characteristics and concentration of allergen-specific IgE-antibodies, no statistically significant differences could be found. Conclusions. The majority of patients rated their allergic symptoms as less severe after AIT. No clear relationship could be demonstrated between pre-treatment allergen-specific IgE concentration, or demographic characteristics, and effect of AIT. There may be other factors underlying the different responses to AIT. Impact statement No correlation exists between profile of allergen sensitization and effect of alleregn immunotherapy. Pre-treatment allergen-specific IgE analysis and outcomes of allergen immunotherapy More research is needed to gain a better understanding of exactly why AIT does not work for all patients. This knowledge will in turn provide opportunities for establishing the optimal dose and method of administration (2). Diagnostic biomarkers help to select the patients who will be the best responders to a specific treatment (2). Analysis of allergen-specific IgE (sIgE) has been proposed as a biomarker for AIT (1). The use of allergen components is of great diagnostic importance to identify the main sensitizing component. One of the aims of this study is to describe the relationship between AIT efficacy and demographic characteristics. Another aim is to study plasma levels of sIgE to grass and birch pollen prior to AIT, measured using the component-resolved, multiplex immunoblot test system, EUROIMMUNE (EUROIM-MUN AG,

Association of allergic patients’ phenotypes with IgE reactivity to recombinant pollen marker allergens

Allergy, 2010

Diagnosis of Type I allergy is based on the documentation of a positive case history, in vivo provocation tests (e.g., skin prick test, nasal, oral and bronchial challenge) and the in vitro detection and measurement of allergen-specific IgE antibodies in patient's serum (1). Natural allergen extracts used for allergy diagnosis and immunotherapy have a number of disadvantages: they contain many different, also nonallergenic proteins and various ill-defined substances (e.g., carbohydrates, enzymes, and fats). The standardization of natural allergen extracts is difficult and the allergen contents and composition of extracts vary from manufacturer to manufacturer and from batch to batch (2-6). Extracts can lack certain allergenic proteins which might have got degraded during the production process and storage and they can be contaminated with proteins from other allergen sources which can deliver false diagnostic results (7). Moreover, allergy tests performed with natural extracts determine only the allergen source a patient reacts with but do not give information about the nature and the number of the disease-eliciting molecules the patient is sensitized to (8). The identification and characterization of allergenic molecules by cDNA cloning allows the large scale production Keywords component-resolved diagnosis; crossreactivity; pollen allergy; recombinant marker allergens; sensitization profile.

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics

World Allergy Organization Journal, 2013

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.