FAQS on when to use Molecular Allergy Diagnosis (MD) in clinical practice

In the last decades there has been a great progress in the field of molecular biology allowing the study of the sensitization to individual allergenic components of an allergenic source, a practice that has been termed Molecular Allergy Diagnosis (MD) or Component Resolved Diagnosis (CRD). The purpose of the present review is to offer the clinician a practical approach to the use of MD by answering frequently asked questions among physicians on how MD can help us improve allergy diagnosis in our daily clinical practice. The article is divided in three sections. First, a brief review on the importance for the clinician to know the main allergens of the different allergenic sources, their structure and their in vitro cross-reactivity before approaching MD (section A). Secondly the core of the review on the usefulness of MD in clinical practice (section B) answering FAQS on the subject, and finally a section (C) on the interpretation and integration of MD with the rest of available tools for allergy diagnosis.

From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack

Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.

96 Sublingual allergen-specific immunotherapy in pediatric patients: biomarkers and molecular allergy diagnostics as predictors of therapeutic success

Background Efficacy of allergen-specific immunotherapy (ASIT) in patients with asthma could be significantly enhanced when physicians have an opportunity to identify those who are most likely to respond, determine when to stop treatment, and predict relapse. Thus, molecular allergy diagnostic is an effective tool that could help to individualize the diagnosis and treatment of asthma by accurate detection of the causative and cross-reactive allergens in pediatric patients. Cytokines are known as reliable diagnostic and prognostic biomarkers for asthma and can be used to evaluate the therapeutic effect. Objectives To evaluate the roles of molecular allergy diagnostic and biomarkers (L-10, IFNγ и TGFβ) as predictors of ASIT efficacy in pediatric patients with asthma. Design/Methods Eighty children aged 5 to 18 years with mild and moderate atopic bronchial asthma were included in the study. Sixty-eight out of 80 (85%) were found to have sensitization to house dust mites Dermatophagoides Pteronyssinus and/or Dermatophagoides Farinae. All these patients underwent molecular diagnostics using ImmunoCAP (Phadia 100) to determine the major (r Der p1, r Der p 2) and minor allergens (r Der p10) of the house dust mites. Twenty-eight patients with mild and moderate asthma were found to have a high sensitivity to these allergens and received SLIT with a mixture of house dust mites (Dermatophagoides Pteronyssinus and/or Dermatophagoides Farinae). To compare the efficacy of SLIT, we evaluated the severity of asthma clinical symptoms on a point scale from 0 to 3, and biomarker levels (IL-10, IFNγ и TGFβ) before and 6 months after SLIT. Twelve healthy children were included in the study as a reference group. Results At the beginning of the study, the average daily score in the SLIT group of 2.5 ± 0.7, and after 6 months of treatment, it decreased to 0.5 ± 0.2. The levels of biomarkers were markedly decreased prior to the treatment, especially TGFβ levels, and normalized at the end of treatment (Tab.1). Conclusion These findings support the efficacy of molecular diagnosis to determine the efficacy of allergen-specific immunotherapy in patients with asthma.

СЮРПРИЗЫ ПИЩЕВОЙ АНАФИЛАКСИИ: СЛУЧАЙ ИЗ ПРАКТИКИ

Анафилаксия - это тяжелая системная реакция гиперчувствительности, которая характеризуется быстрым началом и жизнеугрожающими проблемами со стороны дыхательных путей и кровообращения. В настоящей статье описан клинический случай развития у трехлетнего ребенка поливалентной аллергии с повторными эпизодами пищевой анафилаксии, родившегося и постоянно проживающего в средней полосе России, но имеющего необычный для жителя Урала профиль сенсибилизации. Клинический случай подробно описан с целью продемонстрировать этапы жизни ребенка, на которых, вероятно, сначала формировалась сенсибилизация, а в дальнейшем возникала манифестация клинических симптомов. Определение профиля сенсибилизации с использованием методов компонентной аллергодиагностики (ISAC, ImmunoCAP) показало, что мальчик сенсибилизирован к большому количеству пищевых аллергенов, в том числе к молочным и яичным протеинам белкам хранения арахиса, сои, фундука и кунжута протеинам, относящимся к nsLTP-белкам. Полученные результаты позволили распознать и дифференцировать истинную IgE-опосредованную сенсибилизацию, предложить оптимальную терапевтическую тактику и подобрать элиминационную диету. Применение методов молекулярной аллергодиагностики оказывается полезным в клинической практике в случае ведения пациентов, имеющих поливалентную сенсибилизацию и страдающих, по данным анамнеза, тяжелыми аллергическими реакциями.Anaphylaxis is a severe systemic hypersensitivity reaction that is characterized by rapid onset and life-threatening respiratory and blood circulation problems. We present to your attention a clinical case of the polyvalent allergy development in a three-year-old child with repeated episodes of food anaphylaxis. The child was born and he constantly lives in central Russia, but has a profile of sensitization unusual for a Ural resident. The clinical case is described in detail in order to demonstrate the stages of a childs life, on which sensitization was likely to be first formed, and later the manifestation of clinical symptoms arose. Determination of the sensitization profile by means of the component allergy diagnostics methods (ISAC, ImmunoCAP) showed that the boy is sensitized to a large number of food allergens, including milk and egg proteins storage proteins for peanuts, soy, hazelnuts and sesame proteins related to the nsLTP-proteins. The obtained results made it possible to recognize and differentiate true IgE-mediated sensitization, to propose the optimal therapeutic tactics and to select an elimination diet. Application of molecular allergy diagnostic methods is useful in clinical practice in case of patients with multivalent sensitization and a history of severe allergic reactions.

A complexidade em alergologia pediátrica: o doente polissensibilizado

AIMS: In the present study, the authors intend to demonstrate the advantages of molecular diagnosis in immunoallergology through the description of a clinical case.CASE DESCRIPTION: We present the case of a 9-year-old male, followed by pediatric immunoallergology with the diagnoses of moderate persistent asthma, persistent rhinitis, atopic eczema and food allergy with severe manifestations (several episodes of anaphylaxis). molecular profile of allergic sensitization contributed to better knowledge of the patient, therapeutic and even prognostic adequacy.CONCLUSIONS: The molecular allergy diagnostic tests, according to the analysis of the present case, allows the establishment and escalation in terms of severity of a more individualistic sensitization profile, which is especially important in the patient who is polysensitized and with reports of respiratory and food allergies.