Measuring the stability (and thereby half-life) of TRECs.
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The stability (and thereby half-life) of TRECs.
Secondary outcome
The changes in telomere length of naive T cells in patients treated with the
immune suppressives mycophenolate mofetil and/or azathioprine.
Background summary
T cell receptor excision circles (TRECs) arise as a by-product during VDJ
recombination of T cell receptors in the thymus. TRECs are an important
parameter in many immunological studies to measure T cell production by the
thymus, as well as peripheral T cell division. It is generally assumed that
TRECs are extremely stable and remain present in T cells and their daughter
cells for years - or even lifelong. This assumption is crucial for the
interpretation of TREC data. However, the half-life of TRECs has never been
experimentally determined because this is impossible when T cells undergo cell
division. Therefore, we are planning to measure TRECs in patients using immune
suppressives which inhibit lymphocyte division.
Study objective
Measuring the stability (and thereby half-life) of TRECs.
Study design
This is a cross-sectional, non-interventional study with invasive procedures.
During the study, a blood sample (80 ml in total) will be drawn from each
subject. From this sample, naive T cells will be isolated. From the DNA of
these cells, both the TREC content and telomere length will be determined using
quantitative (q)PCR. Telomere length is a control parameter, since a decrease
in TREC content could either derive from residual cell division (thereby also
decreasing telomere length), or by intrinsic instability of TRECs.
Cell lysates will be used to measure telomerase activity. Telomerase activity
leads to enhanced telomere length, while this would decrease during cell
division.
Study burden and risks
A blood volume of 70 ml, and one red top tube will be drawn (80 ml in total).
If it is impossible to combine this visit with a standard visit to the UMC
Utrecht, an extra visit will have to planned for this study. This is a light
burden. Dialysis patient visit the UMC Utrecht on a regular basis and therefore
will not need an additional visit for this study.
The risk of the single blood draw is very low. For dialysis patients this blood
draw does not come with an additional burden, since the blood will be drawn via
the dialysis needle.
Lundlaan 6
Utrecht 3584 EA
NL
Lundlaan 6
Utrecht 3584 EA
NL
Listed location countries
Age
Inclusion criteria
kidney transplantation(s);
longterm (>10 years) immune suppression by mycophenolate mofetil and/or azathioprine
Exclusion criteria
chronic graft rejection;
thymectomy;
T cell defect(s) prior to transplantation
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 | NL38931.041.12 |