To determine the replication history of DS-B-lymphocytes by KRECs in relation to somatic hypermutation.
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Description of the replication history of DS-B-lymphocytes in relation to
reference groups. This replication history will be presented in divisions per
B-lymphocyte subpopulation.
Somatic hypermutation will be presented as the percentage of mutated V*3-20-J*
allels.
Secondary outcome
Not applicable.
Background summary
The increased frequency of haematological malignancies, autoimmune diseases and
infections in Down Syndrome (DS), and the observed high frequency of hepatitis
B surface antigen carriers, had already led in the 1970s to the hypothesis that
DS is associated with abnormalities of the immune system. Indeed, many
differences between the immune system of DS and non-DS individuals have been
found throughout the years. Most research has been focused on the
T-lymphocytopenia although the decreased numbers of B-lymphocytes are more
profound. Moreover, lower numbers of CD21+, CD23+ and CD27+ B-lymphocyte are
described and the responses to several vaccine antigens are low. These findings
lead to the question whether DS-B-lymphocytes suffer from an intrinsic
B-lymphocyte defect, decreased T-lymphocyte help or both.
The replication history of B-lymphocyte subpopulation can be determined by
kappa-deleting recombination excision circles (KRECs). Per B-lymphocyte
subpopulation (CD5+ B-lymphocytes, naive mature B-lymphocytes, natural effector
B-lymphocytes and memory B-lymphocytes) the amount of divisions will be
determined. These results provide information on the proliferation of
B-lymphocytes caused by either a T-lymphocyte dependent or T-lymphocyte
independent antigen response.
Moreover, by assessing somatic hypermutation more knowledge will be obtained on
the qualitative antibody response.
Study objective
To determine the replication history of DS-B-lymphocytes by KRECs in relation
to somatic hypermutation.
Study design
An observational study will be performed. During a scheduled venipunction for
medical purposes an extra 40 ml will be obtained. The medical history will be
noted as well.
Study burden and risks
Patients will not experience any direct benifits from participation in this
study. The blood will be obtained during a scheduled venipunction for medical
purposes. Therefore the harm is limited as much as possible. The expected gain
in knowledge on the DS immune system justifies this limited harm.
Postbus 90153
5200ME 's-Hertogenbosch
NL
Postbus 90153
5200ME 's-Hertogenbosch
NL
Listed location countries
Age
Inclusion criteria
Down syndrome, age >7 years
Exclusion criteria
Infectious disease or treated for malignancy
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 | NL31797.028.10 |