IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen

Assessment of Google Trends terms reporting allergies and the grass pollen season in Ukraine

International audienceBackground: Grass pollen allergy is an important trigger for the development of respiratory disorders. Defining the grass pollen season onset is critical for correct allergy diagnosis and personalized therapy. The development of a pan-European sentinel network for allergic diseases has raised the problem of translating the Google search terms into different European languages as well as defining specific pollen season characteristics in different regions. Grass pollen allergy was investigated due to high allergenicity and wide expansion of grass pollen in Europe. Objectives: The aim of this study was to examine which translations of “hay fever”, “grass”, and “rhinitis” could be used in the native Cyrillic languages, especially in Ukrainian and Russian, and to compare the seasonality of allergic respiratory queries in Ukraine with the grass pollen counts. Methods: Google Trends (GT) was used to search Google queries concerning grass pollen allergy: “allergy”, “hay fever”, “runny nose”, “grass”, “asthma”, and “pollen”. The Cyrillic terms in Ukrainian and Russian were used. The search was done for the period from 2013 to 2017. Pollen collection from 2013 to 2016 was conducted using volumetric methods. Average daily temperatures were obtained from http://gismeteo.ua. Correlations were assessed by Spearman (R) test. Results: The Ukrainian Google users searched the Cyrillic equivalents for “runny nose”, “grass”, and “asthma”. Due to the GT queries profile, Ukraine had a “D” pattern according to the classification, developed by Bousquet J et al (2017). In Ukraine, the Poaceae pollen season generally occurred between the second ten-day period of May and the last ten-day period of July. The Poaceae pollen season started with a concentration of pollen grains of 8.0 m−3. This concentration provoked the growth of GT “grass”, “allergy”, “hay fever”, and “asthma” queries. Conclusions: The terms “grass”, “allergy”, “hay fever”, and “asthma” (in their Cyrillic equivalents) are required in Ukraine to account for the grass pollen exposure by GT. The study of GT may be a useful tool to make an assessment of the grass pollen season for the prevention and minimization of exposure to significant grass pollen concentrations

Dogmas, challenges, and promises in phase III allergen immunotherapy studies

The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries. Moreover, most of these AIT products are provided on an individual patient basis as named patient products (NPP) in Europe, while individualized preparations of (mixed) allergenic extract vials for subcutaneous administration (compounding) is common practice in the US. AIT products are generally considered safe and well tolerated, but the major practical clinical development challenge is to define the optimal dose and prove the efficacy and safety of these products using state-of-the art Phase II and pivotal Phase III studies. In planning Phase II-III AIT studies, a thorough understanding of the study challenges is essential (e.g. variability and non-validated status of subjective primary endpoints, limitations of pollen season definitions) and dogmas of these products (e.g., for sublingual immunotherapy (SLIT) trials double-blinding conditions cannot be maintained, resulting in stronger placebo responses in the active treatment group and inflated treatment effects in Phase III). There is future promise for more objective biomarker endpoints (e.g. basophil activation (CD63 and CD203c), subsets of regulatory dendritic, T and B cells, IL-10-producing group 2 innate lymphoid cells; alone or in combination) to overcome several of these dogmas and challenges; innovation in AIT clinical trials can only progress with integral biomarker research to complement the traditional endpoints in Phase II-III clinical development. The aim of this paper is to provide an overview of these dogmas, challenges and recommendations based on published data, to facilitate the design of Phase III studies and improve the evidence basis of safe and effective AIT products. Keywords: Allergen immunotherapy; Biomarker; Blinding; Phase III; Placebo effect

Structural and Functional Properties of IL-4δ2, an Alternative Splice Variant of Human IL-4

Structural and functional properties of recombinant IL-4δ2, a naturally occurring splice variant of human IL-4 with a deletion of the loop region 22−37, have been analyzed. IL-4δ2 has α-helical structure and most likely preserves the “up−up−down−down” topology typical of the four-helix-bundle cytokines. IL-4δ2 interacts specifically with the α chain of IL-4R and competes effectively with IL-4 for the common binding sites. Thus, IL-4δ2 may act as a regulator of the cytokine net, being the natural antagonist of IL-4