Molecular-based Allergy Diagnostics Research Articles

An update on the prevalence and diagnosis of cat and dog allergy – Emphasizing the role of molecular allergy diagnostics

The clinical presentation of cat and dog allergy vary from discomfort caused by rhinoconjuncitivitis to severe asthma. Exposure to allergens from these animals is ubiquitous and allergic sensitization to cat or dog affect up to 25% of all children and adults, but allergic sensitization does not always cause symptoms. The introduction of molecular-based allergy diagnostics has improved the possibility to characterize the allergic patient in greater detail. However, the full clinical potential of using molecular allergology in the diagnosis, characterization and treatment of patients with allergy to cats and dogs has not yet been established, although significant progress has been made during the last decade, which will be reviewed in detail in this paper.

Food-dependent exercise-induced reactions: lessons from a 15-year retrospective study.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a life-threatening disorder in which the signs and symptoms of anaphylaxis occur if physical exertion occurs within a few hours of exposure to a food. The aim of this study was to characterise patients diagnosed with FDEIA and related disorders. A retrospective review of electronic clinical data from 2001 to 2016 was carried out. Fifty-seven cases were identified and analysed to establish clinical features, triggering factors and sensitisation patterns. The number of patients per annum diagnosed with FDEIA or related reactions increased from 1 in 2001 to 18 patients in 2016. Sixty-nine percent reported systemic symptoms consistent with anaphylaxis, and 31% had skin manifestations only. In 33% of cases, the level of triggering exercise was mild. Forty-four percent of patients were sensitised to the omega-5-gliadin fraction of wheat. FDEIA is an increasingly recognised serious allergic disease. The clinical diagnosis is supported by targeted sensitisation testing and molecular-based allergy diagnostics. These tools allow implementation of effective dietary and lifestyle modifications that mitigate against future serious reactions. Given the limited access to physicians with specialist allergy training in Ireland, increased awareness of this condition amongst sports medicine specialists and general physicians is required.

Phleum pratense molecular pattern across Italy.

Introduction. Phleum pratense (Timothy grass) is the most frequent cause of grass allergy in Europe. Molecular-based allergy diagnostics have been recently introduced in the clinical practice, allowing to define and characterize exactly the sensitization profile. Aim of the study. The present study was aimed to investigate the possible relationships between Graminaceae pollen data and the pattern of IgE reactivity to different allergen components across Italy. Methods. Pollen data, including duration and quantity, were recorded over a 10-year period in 24 Italian centres located along the Italian peninsula. Phl p molecular patterns (Phl p 1, 5, 7, 12) were evaluated in 4 different Italian geographical areas. Results. There were significant differences about pollen count and sensitization prevalence across Italy. Different molecular patterns were defined considering the different Italian locations. Conclusion. This study demonstrates that Phleum pratense sensitization is relevant in Italy, but there are significant geographical variations variations as far as pollen exposure and pattern of IgE reactivity to the considered allergen components are concerned. This information may have clinical relevance in managing patients allergic to grass pollen.

Debates in allergy medicine: specific immunotherapy efficiency in children with atopic dermatitis

Allergen specific immunotherapy (AIT) has been the only pathogenetically relevant treatment of IgE-mediated allergic diseases (ADs) for many years. The use of AIT for atopic dermatitis (AD) treatment is dubious and has both followers and opponents. The improvement of subcutaneous AIT (SCIT) and introduction of Sublingual immunotherapy (SLIT) gives prospects of their application both for adults and children suffering from AD. This review presents results of scientific research, system and meta-analyses that confirm the clinical efficacy of AIT for children with AD who has the sensitization to allergens of house dust mite, grass and plant pollen suffering from co-occurring respiratory ADs and with moderate and severe course of allergic AD. There have been analyzed the most advanced achievements in AIT studies as well as there have been specified the unmet needs in AD. The preliminary diagnostics of IgE-mediated AD and pathophysiological disorders, including immune ones, will allow a doctor to develop appropriate comprehensive treatment algorithm for children’s AD aimed at its correction. The including of AIT to the children’s comprehensive therapy program is reasonable only if AD has the allergic form. It is necessary better to design the randomized research studies and to acquire extended clinical practice in children with AD. Use of the successes of molecular-based allergy diagnostics will help to optimize and personalize the process of selecting the necessary allergens to determine the most appropriate vaccines for children considering the results of the allergen component diagnostics. The strategy of treatment of children with AD in future will be based on individual target therapy.

Cow’s milk and hen’s egg allergy: what do molecular-based allergy diagnostics have to offer?

Cow’s milk and hen’s egg are among the most common triggers of IgE-mediated allergic reactions in childhood. Since not all IgE sensitizations are clinically relevant, it is important to confirm or exclude manifest allergy. Thus, the burden of an elimination diet will be restricted to only those cases where such a measure is essential. A number of proteins have been identified in cow’s milk and hen’s egg as single allergens (Bos d 1–12 in cow’s milk and Gal d 1–6 in hen’s egg). However, measuring IgE to these single allergens predicts neither clinical relevance nor prognosis of the individual allergy. In terms of ascertaining whether cooked hen’s egg is tolerated, measuring sIgE to ovomucoid (Gal d 1) can be useful. Measuring sIgE to lysozyme (Gal d 4) can be helpful in deciding whether lysozyme-treated foodstuffs (e.g., cheese) should be avoided. Single allergen determination is not able to answer the question of whether cow’s milk or hen’s egg are tolerated in baked form (e.g., in muffins). If the foodstuffs in question are routinely tolerated in baked form, the prognosis is favorable.

Molecular-based allergy diagnosis of allergic bronchopulmonary aspergillosis in Aspergillus fumigatus-sensitized Japanese patients.

Distinguishing between patients with allergic bronchopulmonary aspergillosis (ABPA) and Aspergillus fumigatus (Af)-sensitized asthmatic patients without ABPA is sometimes difficult owing to the IgE-cross-reactivity between Af and other fungal allergens. To establish the usefulness of molecular-based allergy diagnostics using allergen components from Af in distinguishing ABPA from Af-sensitized asthma without ABPA. Sera from Japanese patients with ABPA (n=53) and Af-sensitized asthma without ABPA (n=253) were studied. The levels of IgE and IgG antibodies to allergen components from Af and IgE antibodies to different fugal allergen extracts were measured by ImmunoCAP. Comorbid atopic dermatitis (AD) was taken into consideration in the sensitization profile analysis. Patients with ABPA possessed significantly higher levels of IgE antibodies to Asp f 1, and Asp f 2 than asthmatic patients without ABPA. The areas under the receiver operating characteristic curves for the levels of IgE to Asp f 1 and Asp f 2 as diagnostic markers of ABPA were 0.75 and 0.78, respectively. The presence of IgE positivity to Asp f 1 and/or Asp f 2 resulted in increased sensitivity while losing little specificity. Comorbid AD was associated with higher levels of IgE to Asp f 6 (manganese superoxide dismutase from Af, a ubiquitous pan-allergen in fungi) and low but positive levels of IgE to other Af-components, which hampered the serological discrimination of ABPA. The levels of IgE to Asp f 1 and/or Asp f 2 can effectively differentiate ABPA from Af-sensitized asthma, suggesting that the amounts of IgE specific for these molecules are markers for genuine Af-sensitization in ABPA. However, comorbid AD must be taken into consideration in the interpretation of high IgE to Asp f 6. Establishing of IgE-sensitization profiles using panel of Af-allergen components provides valuable information for distinguishing genuine vs. cross-reactive sensitization in Af-sensitized patients.

Allergy to furry animals: New insights, diagnostic approaches, and challenges

The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. Aworkshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components.

Severe childhood asthma and allergy to furry animals: Refined assessment using molecular‐based allergy diagnostics

Allergy to cats and dogs and polysensitization towards these animals are associated with severe childhood asthma. Molecular-based allergy diagnostics offers new opportunities for improved characterization and has been suggested to be particularly useful in patients with polysensitization and/or severe asthma. The aim was to use extract- and molecular-based allergy diagnostics to compare patterns of IgE sensitization towards aeroallergens in children with problematic severe and controlled asthma. Children with a positive ImmunoCAP towards any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish study on severe childhood asthma. Severe (n=37, age 13years) and controlled (n=28, age 14years) asthmatics underwent assessment of allergic sensitization by ImmunoCap (kUA /l) and immunosolid-phase allergen chip (ISAC). In addition, Asthma Control Test, spirometry and a methacholine challenge were performed. Children with severe asthma had lower asthma control (p<0.001) and FEV1 (p=0.001) and more bronchial hyper-responsiveness (p=0.008) in spite of high doses of inhaled steroids (≥800μg budesonide). Children with severe asthma displayed higher levels of IgE antibodies towards cat (17 vs. 3.9, p=0.027), dog (3.8 vs. 1.2, p=0.012) and horse (7.4 vs. 0.7, p=0.014). Sensitization towards Can f 2 (22% vs. 0%, p=0.009) and Equ c 1 (51% vs. 25%, p=0.03) was more common in severe asthma. IgE levels towards Equ c 1 correlated with asthma control (r=-0.41, p=0.04). Children with severe allergic asthma had higher sIgE levels to cat, dog and horse. Molecular-based allergy diagnostics revealed a more complex molecular spreading of allergen components in children with the most severe disease.

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

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.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.