Project description DEENESFRITPL Uncovering the mechanisms of anaphylactic reactions to wasp bites Anaphylactic reactions to insect bites can be fast and fatal unless treated with venom immunotherapy (VIT). With immune hypersensitivity reactions occurring years after treatment termination, scientists of the EU-funded MITafterVIT project are working to understand the underlying molecular mechanisms of maintained immune tolerance (MIT). Their experimental approach is based on the observation that people with a clonal mast cell disease (CMD) who experience wasp venom anaphylaxis do not maintain immune tolerance after VIT termination. In particular, the project is investigating a mutation in the tyrosine kinase receptor KIT in immune cells and how it affects immune tolerance. The project's findings will be beneficial for individuals experiencing anaphylaxis but can potentially apply to other types of allergies. Show the project objective Hide the project objective Objective Anaphylaxis is the most severe form of a systemic hypersensitivity reaction, which can be fatal within minutes after exposure to a trigger such as wasp venom. VIT has been the only treatment available to prevent subsequent anaphylactic wasp-sting reactions even years after treatment termination.The goal of this project is to understand molecular mechanisms of maintained immune tolerance (MIT) after completing venom immunotherapy (VIT). We aim to find biomarkers for MIT that could be specifically triggered to increase efficiency of VIT. In contrast to wasp venom anaphylactic patients of the general population, wasp venom anaphylactic patients with a clonal mast cell disease (CMD) do not maintain immune tolerance after VIT termination. These patients carry a clonal D816V point mutation in the tyrosine kinase receptor KIT. We hypothesize that the MIT in wasp venom anaphylactic CMD patients is dysregulated due to the carriage of KIT D816V mutation in immune cells. We will, therefore, compare blood plasma proteins and blood cells of venom-induced anaphylaxis patients with a CMD to patients without a CMD. This project addresses our hypothesis with three specific objectives: Firstly, we will identify plasma proteins (in work package 1; WP1) and, secondly, blood cell types (WP2) that are crucial for MIT. Thirdly, we will study the role of the identified candidates from WP1 and WP2 in maintaining immune tolerance (WP3) and investigate whether or not the detected dysregulations are due to KIT D816V (WP3).We estimate that our results will, therefore, be directly relevant for 0.3% of the European population who experience anaphylaxis and bares potential to be also beneficial for patients suffering from other allergic diseases, which account for a significant part of the population worldwide. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicineimmunologyimmunotherapy Keywords anaphylaxis venom immunotherapy clonal mast cell disease Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator KAROLINSKA INSTITUTET Net EU contribution € 191 852,16 Address Nobels vag 5 17177 Stockholm Sweden See on map Region Östra Sverige Stockholm Stockholms län Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
