To investigate the interrelatedness between clonal hematopoiesis of indeterminate potential (CHIP) and trained immunity.
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
60 ml of blood will be drawn by venepuncture to measure cytokine production
capacity and the susceptibility to develop trained immunity.
Secondary outcome
In addition, within the subjects with the driver mutations, single cell RNA
sequencing will be performed to explore the hypothesis that monocytes with a
mutation are more amenable to trained immunity.
Background summary
In the past years, two mechanisms of innate immune cell activation have been
discovered that both contribute to the development of atherosclerotic
cardiovascular disease: clonal hematopoiesis of indeterminate potential (CHIP)
and trained immunity. CHIP describes the age related occurrence of somatic DNA
mutations in myeloid progenitor cells which confer a survival benefit to the
cell, resulting in circulating monocyte clones. These driver mutations most
commonly occur in the epigenetic enzymes DNMT3A and TET2. Trained immunity
described the phenomenon that monocytes can build a long-term proinflammatory
phenotype after brief exposure to inflammatory stimuli. This is also mediated
by epigenetic reprogramming.
Study objective
To investigate the interrelatedness between clonal hematopoiesis of
indeterminate potential (CHIP) and trained immunity.
Study design
Exploratory observational single centre study
Study burden and risks
The subjects will have no benefit. Sixty mls of blood will be drawn which will
not have any adverse consequences for the participants.
Geert Grooteplein Zuid 10
Nijmegen 6225 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6225 GA
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- Participant of the 300OB study
- Mutation in TET2, DNMT3A, or no driver mutation
- Informed consent
Exclusion criteria
- Current use of immunomodulatory drugs.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL72552.091.20 |