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Opinion statement Allergen-specific immunotherapy (AIT) is the only treatment of IgE-mediated allergies so far that has a sustained effect on clinical symptoms and can modify the course of the disease. It is an allergen-specific treatment and therefore requires the correct identification of the disease-causing allergens. Furthermore, AIT is a time-consuming treatment for which the efficacy is dependent on several factors. Therefore, diagnostic tests and biomarkers are needed that facilitate (1) selection of the correct allergens according to the patient’s individual sensitization profile and (2) to monitor the effects of AIT. This can provide support for the decision to continue, modify, or discontinue vaccination. One significant mechanism of action of AIT is the induction of allergen-specific antibodies that compete with IgE for the binding to allergen molecules, hence referred to as blocking antibodies. It was shown in several studies that the induction of blocking antibodies by AIT, and their specificity can be measured by allergen microarrays. Inhibition of allergen-specific IgE binding by blocking antibodies can also be determined by microarrays and is associated with changes in clinical parameters or other in vivo and in vitro assays demonstrating efficacy of AIT. Furthermore, allergen microarrays allow determination of IgE sensitizations towards a comprehensive set of allergen molecules and therefore are well suited for identifying the disease-causing allergens for correct prescription of AIT. Thus, diagnostic tests based on microarrayed allergens can be useful in determining the correct prescription of AIT and can be used to monitor efficacy of AIT.

Background In Africa, peanuts are frequently consumed, but severe allergic reactions are rare. We investigated immunological patterns of clinical tolerance to peanut in peanut-sensitized but asymptomatic patients from central Africa compared to peanut-allergic and peanut-sensitized but asymptomatic patients from Sweden. Methods Sera from allergic patients (n = 54) from Zimbabwe sensitized to peanut but without allergic symptoms to peanut, and sera from peanut-allergic (n = 25) and peanut-sensitized but asymptomatic (n = 25) patients from Sweden were analyzed toward peanut allergen components (Ara h 1–3, 6, 8–9) and other allergen molecules from important allergen sources using microarray. IgE to Ara h 2 peptide epitopes was analyzed, and allergenic activity was assessed by basophil activation assay. Results Forty-six percent of the African and all peanut-allergic Swedish patients showed IgE toward one of the highly allergenic peanut allergens (Ara h 1–3, 6, 9). However, 48% of the African patients had IgE to cross-reactive carbohydrate determinants (CCDs) with low allergenic activity and 60% of the Swedish asymptomatic patients had IgE against the PR protein Ara h 8. IgG and IgG4 specificities and levels could not discriminate between the African asymptomatic and Swedish peanut-allergic patients. Asymptomatic patients almost lacked IgE to Ara h 2 peptides, which were recognized by peanut-allergic patients. Peanut IgE from peanut asymptomatic patients showed poor allergenic activity compared with IgE from peanut-allergic patients. Conclusions Natural clinical tolerance to peanut in the African patients can be caused by IgE to low allergenic peanut components and by poor allergenic activity of peanut-specific IgE.

Background Carvajal syndrome is an autosomal dominant or autosomal recessive disorder, manifesting with dilated cardiomyopathy, woolly hair, and palmoplantar keratoma. Additional manifestations can be occasionally found. Carvajal syndrome may be due to mutations in the desmocollin-2, desmoplakin, or plakophilin-2 gene. Methods and results We report a family with Carvajal syndrome which additionally presented with hypoacusis, noncompaction, recurrent pharyngeal infections, oligodontia, and recurrent diarrhoea. Father and brother were also affected and had died suddenly, the father despite implantation of a cardioverter defibrillator (ICD). Genetic studies revealed the novel pathogenic mutation c.1678A > T in the desmoplakin gene resulting in the amino acid change Ile to Phe at position 560 in the index case and her brother. The index case underwent ICD implantation recently. Conclusion Phenotypic manifestations of Carvajal syndrome are even broader than so far anticipated, the number of mutations in the desmoplakin gene responsible for Carvajal syndrome is still increasing, and these patients require implantation of an ICD as soon as their diagnosis is established.

Background The green area in Tashkent-city in Uzbekistan has been re-organized during the last two decades. It covers approximately 35% of the total area and includes classical vegetation present in Central Asia such as saltwort and newly planted species such as Bermuda grass. The knowledge of the molecular sensitization profiles of allergic patients is essential for the correct treatment with allergen specific immunotherapy but has not been established for allergic patients in the Central Asian area. Objective The aim of this study was to determine the IgE-sensitization profile towards pollen allergens in patients with respiratory allergy from Tashkent. Methods Fifty adult patients with allergic rhinitis and/or asthma were tested using an allergen micro-array containing 112 different allergen molecules (ImmunoCAP ISAC; Thermo Scientific). Results We found that the major Bermuda grass pollen allergen, Cyn d 1 and the major saltwort allergen Sal k 1 were most frequently recognized allergens. More than 42% of the patients displayed IgE reactivity to Cyn d 1 and the percentage was even higher in the group suffering from allergic asthma (n=12) (i.e., 66%). Sal k 1 was recognized by 46% of the patients and by 50% of the patients with asthma. The other pollen allergens were recognized less frequently. Interestingly, more than 20% of patients showed IgE cross-reactivity with profilins from grass pollen, weed pollen and birch pollen whereas no patient mounted IgE reactivity to the major birch pollen allergen, Bet v 1. Conclusion The results of the IgE profiling identify grass pollen and in particular Bermuda grass and salkwort as the most important pollen allergen sources in Tashkent. Although approximately 20% of the patients reacted with birch pollen profilin, none of the patients reacted with the major birch pollen allergen, Bet v 1, indicating that these patients had no genuine sensitization to birch. These data show that the molecular sensitization profile towards pollen allergens in Central Asia is an in-print of the local flora and indicates how important allergen micro-array analysis is for the selection of the correct immunotherapy treatment. This study was supported by the Austrian Science Fund (FWF), American Austrian Foundation (AAF) and was performed in the framework of International Network University for Molecular Allergology and Immunology.

Allergy diagnosis based on purified allergen molecules provides detailed information regarding the individual sensitization profile of allergic patients, allows monitoring of the development of allergic disease and of the effect of therapies on the immune response to individual allergen molecules. Allergen microarrays contain a large variety of allergen molecules and thus allow the simultaneous detection of allergic patients' antibody reactivity profiles towards each of the allergen molecules with only minute amounts of serum. In this article we summarize recent progress in the field of allergen microarray technology and introduce the MeDALL allergen-chip which has been developed for the specific and sensitive monitoring of IgE and IgG reactivity profiles towards more than 170 allergen molecules in sera collected in European birth cohorts. MeDALL is a European research program in which allergen microarray technology is used for the monitoring of the development of allergic disease in childhood, to draw a geographic map of the recognition of clinically relevant allergens in different populations and to establish reactivity profiles which are associated with and predict certain disease manifestations. We describe technical advances of the MeDALL allergen-chip regarding specificity, sensitivity and its ability to deliver test results which are close to in vivo reactivity. In addition, the usefulness and numerous advantages of allergen microarrays for allergy research, refined allergy diagnosis, monitoring of disease, of the effects of therapies, for improving the prescription of specific immunotherapy and for prevention are discussed. This work was supported by the European Commission’s Seventh Framework Programme under grant agreement No. 261357 and in part by project F4605 of the Austrian Science Fund (FWF) and the Christian Doppler Research Association, Austria