Subproject 6 - Mechanism and markers for remission of allergic diseases: Systematic detection of mechanisms and markers for allergy remission in children
Project leader Prof. Dr. med. Michael Kabesch
Although allergies are generally viewed as a chronic, persistent disease, it has been shown that natural remission is possible and more frequent in children and youth (app. 5% per year) than in adults, where remission rarely occurs (1-2% per year). This is highly relevant, since understanding mechanisms that contribute to remission may teach us how allergy development and progression can be stopped “naturally” and thus, this insight may provide novel avenues for treatment and even prevention of allergies.
The main goal of this project is to identify and characterize the mechanisms of asthma and allergy remission either spontaneously or after immunotherapy in late childhood and adolescence.
We hypothesize that children who lose their allergic diseases have distinct molecular signatures which we could be able to determine, either before the remission (predictors) or after the remission (biomarkers).
First step: Collecting the biomaterials from two groups of patients:
- To define molecular networks in natural remission, the samples from participants including atopic asthma, allergic rhinitis, and atopic dermatitis will be collected in two different time points - first when the doctors make the decision to stop the treatment (predictors) and the second time 1 year after that if there are no symptoms (biomarkers).
- To determine mechanisms of remission due to immunotherapy samples of subjects included - atopic asthma and allergic rhinitis will be collected in two different time points - first when they want to start the immunotherapy (predictors) and the second - 1 year after the first time point, if there are no symptoms (biomarkers).
Second step: Defining remission signatures by investigating:
- Genetics: Assess genetic profiles of remission by Genome Wide Association Study (GWAS).
- Epigenetics: Investigate the epigenetic regulation by methylation pattern in blood, skin, and respiratory epithelia
- Transcription: Evaluate expression profiles of targeted genes at the protein /mRNA level in various samples – blood, sputum, nasal scraping.
- Metabolomic analysis: Understand the metabolomics profile of serum and stool samples
- Microbiome analysis: Determine microbiome patterns of stool and skin scraping samples
Third step: validation and replication:
We will validate and replicate molecular signatures of remission, identified in our population in the first step, with the data from the already established two cohorts including Study on Occupational Allergy Risk (SOLAR) cohort (n=1000) and the Multicentre Asthma Genetics In Childhood (MAGIC) study cohort (n= 800), where children have been recruited during childhood and followed into adulthood..
Finally: The integration of the different layers of information in this project is challenging: phenotype, environmental factors, genetics, transcriptomics, epigenomics, and metabolomics. For the remission of an individual child, many factors might be important. Here we will use a multilayer network model in which the omics and clinical variables are organized into a network to understand disease mechanisms.
Prof. Michael Kabesch's team includes pediatricians specialized in pulmonology and allergology, biologists, geneticists, biostatistics and IT specialist.Principal Investigator Prof. Dr. med. Michael KabeschProf. Michael Kabesch is a pediatrician, pulmonologist and allergist. He is the head of the Department of Pediatric Pulmonology and Allergology at the University of Regensburg. He is a group leader of several national and international projects that investigate genetic and epigenetic effects of allergies and respiratory diseases, with a focus on gene and environment interaction analysis and functional genomics.