Hereditary Hemorrhagic Telangiectasia
Conditions
Brief summary
The possibility of body donation in hereditary hemorrhagic telangiectasia (HHT) means that human tissue samples with and without vascular malformations can be analyzed. The aim is to gain insights into the disease mechanism.
Detailed description
HHT is also known as Osler's disease or Rendu-Osler-Weber syndrome and is inherited in an autosomal dominant manner. With a prevalence of 1 in 5,000 - 10,000 people, it is one of the relatively common rare diseases. In terms of molecular biology, affected individuals have a disorder of physiological angiogenesis, resulting in pathological vascular connections, so-called arteriovenous malformations. In principle, vascular changes in the context of HHT can affect all organ systems, but there are various predilection sites such as the skin and mucous membranes, liver, lungs, gastrointestinal tract and brain. In preliminary work, we were able to show that in addition to the known mutations in the TGFβ signaling pathway, further trauma or previously unknown events must occur locally in order for the vascular short circuits to form. However, the exact disease mechanisms are still unclear. Obtaining human tissue samples is difficult due to ethical concerns (taking samples from living patients could lead to a worsening of the disease). The aim of this project is to analyze structural changes in tissue samples with and without vascular malformations.
Interventions
OTHERbody donation in HHT
Body donation in HHT
Sponsors
University Hospital, Essen
University Hospital Marburg
Johannes Gutenberg University Mainz
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Genetic analyses (e.g. using qPCR, analyses of the genome and transcriptome), protein analyses (e.g. using Western blot) and immunohistochemical analyses (cryo- and PFA-fixed) of tissue samples from various organs will be carried out. Genome editing (e.g. using CRISPR/Cas9) will be applied. It is planned, for example, to generate human induced pluripotent stem cells (hiPSCs) from the biomaterials (in particular from fibroblasts and blood cells (PBMCs)). In addition, morphological imaging (3D) of the organs (including lungs and brain) is planned.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* positiv genetic testing for HHT and/ or at least three fulfilled Curacao Criteria * older than 18 years
Exclusion criteria
* missing inclusion criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in immune and endothelial cells in tissue with and without telangiectasia in HHT | after the patients who gave informed consent died their body will be donated to the Institute of Anatomy of the University Hospital Essen, samples will be taken until the body is cremated (regularly within 12 months) | Analysis of the differences in tissue with and without telangiectasia in HHT, e.g. immunfluorescence staining of tissue / bone with endoglin-/ alk 1- antibodies and quantitative analysis of endoglin/ alk1 lacking cells such as immune cells or endothelial cells |
Countries
Germany
Contacts
CONTACTFreya Droege
Outcome results
None listed