To quantify leukocyte turnover, characterize immune phenotype and function, determine T-cell receptor repertoire, and measure soluble immune factors in bone marrow and blood of healthy adults.
ID
Source
Brief title
Condition
- White blood cell disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The average turnover of different immune cell subsets in bone marrow of healthy
human adults during homeostasis.
Secondary outcome
- The average turnover and lifespan of antigen-specific T cell subsets in bone
marrow and paired blood;
- The phenotype of immune cells in bone marrow and paired blood based on flow
cytometric markers (percentage positive and mean fluorescence intensity).
- The function of immune cells in bone marrow and paired blood based on in
vitro stimulation assays, e.g. in IFN-g or TNF-a production.
- Concentration of factors in plasma and bone marrow and paired blood that can
influence leukocyte dynamics, such as growth and survival factors, infection
parameters, and viral factors.
- Comparison of the T-cell receptor (TCR) repertoire between blood and bone
marrow;
- Determination of the phenotype of adaptive NK cells in blood and bone marrow
using scATAC-seq.
Background summary
Most insights into human immune cells have been based on cells isolated from
the blood. There are strong indications, however, that the bone marrow provides
a special niche for immune cells. It is the place where many leukocytes find
their origin, and it has been suggested that antigen-experienced T- and B-cells
in the bone marrow are protected from death and thereby retain long-term
immunological memory. In this research, we want to investigate the lifespan of
leukocytes in bone marrow of healthy adults and gain insight in the differences
between leukocytes in peripheral blood versus bone marrow.
Study objective
To quantify leukocyte turnover, characterize immune phenotype and function,
determine T-cell receptor repertoire, and measure soluble immune factors in
bone marrow and blood of healthy adults.
Study design
Investigator-driven, multicentre, longitudinal, non-interventional, pilot study
with invasive procedures and imposed rules of conduct.
Study burden and risks
Participants will drink heavy water for a maximum of 9 weeks. They will also
donate bone marrow after a study-independent hip or knee replacement surgery,
undergo 1-5 venepunctures, and collect multiple saliva/urine samples. The risks
related to deuterated water intake, venepuncture, and saliva/urine donation are
low. Collection of bone marrow (rest material) after the hip or knee
replacement surgery does not add additional risks to the already scheduled
elective surgery. Even though the physical burden and risks of this study are
minimal, the personal burden is higher: participants will have to invest time
and energy to visit the hospital, donate blood, saliva/urine, and bone marrow,
and drink daily heavy water at home. There is no direct benefit in
participation and the risks are minimal.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
Elective hip or knee replacement surgery, older than 55 years of age
Exclusion criteria
(Pathological) fracture as surgery indication, chronic infection, daily use of
immuno-modulatory 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 | NL74992.041.20 |