To gain insight in the regulation of immune responses in patients with CVID
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Quantification and characterisation of apoptosis in T and B cells
2. Quantification and functional determination of regulatory T cells
3. Function of the thymus
Secondary outcome
1. The differences in the 3 abovementioned outcome parameters between healthy
controls, CVID patients and XLA control patients for both the pediatric and
adult population.
2. The differences in the 3 abovementioned outcome parameters between subgroups
of CVID patients, namely patients with and without auto immune symptoms, also
within the pediatric and adult population.
3. Correlation between the function of the thymus and the amount of regulatory
T cells.
4. Correlation between regulatory T cells and apoptosis.
Background summary
CVID (Common Variable Immunodeficiency, a primary immune disease) is an immune
disease with an unknown cause. Although the disease is relatively rare
(incidence of some tens per year in the Netherlands), CVID remains important,
due to the life-long duration, high morbidity and possible mortality. The
hallmark of CVID is an impaired antibody production, as a result of functional
B cell defects. This makes patients prone to infections and most research
therefore focusses on those B cells.
Additionally, a significant part of the CVID population suffers from a
distorted immune regulation, leading to auto immune disease. Platelets and red
blood cells can be attacked by auto-antibodies, causing potentially severe
disorders such as anemia and an increased risk of bleedings.
It is difficult to understand why patients on one hand cannot produce
sufficient antibodies to fight infections, while on the other hand they are
able to produce antibodies against their own cells. One explanation could be
that the programmed cell death or apoptosis of B cells (or of the T cells that
help them) is disturbed. It is possible that self-reactive cells are not
cleared properly, or that other cells die too easily, for example the
regulatory T cells. These T cells are able to suppress immune responses. When
there function is impaired, an uncontrolled immune response perpetuates,
eventually causing autoimmunity. Another possibility is that the thymus does
not produce enough regulatoy T cells, also leading to insufficient suppression
of immune responses.
Study objective
To gain insight in the regulation of immune responses in patients with CVID
Study design
Cross-sectional patient control study
Study burden and risks
Minimal burden and risks: Of the patients and healthy controls, 20ml (children)
or 40ml (adults) blood will be taken only at the moment when venipuncture has
to be performed already, namely to supplete immunoglobulins or for routine
blood controls (patients) and prior to surgical procedure that is not related
to immune disease (pediatric controls).
Lundlaan 6
3584 EA Utrecht
Nederland
Lundlaan 6
3584 EA Utrecht
Nederland
Listed location countries
Age
Inclusion criteria
Diagnosis of CVID; based on recurrent respiratory tract infections, decreased total serum IgG (<-2SD) and impaired specific antibody production after vaccination. Both patients with and without auto immune phenomena will be included.
Diagnosis of XLA; based on the (almost complete) absence of B cells and a mutation in the Btk gene.
Exclusion criteria
Both patients groups: uncertainty about the diagnosis. Acute and/or severe infections at the moment of inclusion.
XLA patients: existence of auto immune symptoms
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 | NL22095.041.08 |