Investigation of the blood B cell compartment in family members of CVID patients (with and without a CVID family history) to identify or exclude B-cell defects and to improve our insight into a potential familial background of CVID.
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Disturbances in the composition of the blood B cell compartment with special
attention for the absolute numbers and relative distribution of naive B cells,
memory B cells, plasma cells and their various subsets.
Secondary outcome
How these aberrancies are distributed over the family members and whether the
ab-errant B-cell and T-cell patterns are comparable between family members;
To select families eligible for a new study to investigate the genetic
background and pathophysiology of CVID.
Background summary
Only in 10% of CVID patients a monogenetic disorder is identified and directly
associated with the disease. However, in approximately 30% there is a positive
family history. To understand the mechanism of disease of unexplained CVID it
is important to investigate to what extend family members have an affected B
cell compartment in relation to the index case. Recently, high dimensional and
standardized flowcytometry studies (within the EuroFlow consortium) have
demonstrated that absolutely no plasma cells are detectable in blood of CVID
patients. In addition, major aberrancies are observed in the memory B cell
compartment while the naïve B cell compartment might be normal or slightly
reduced. In part of the CVID patients also the T cell CD4+ compartment appears
to be affected.
We hypothesize that in family members of CVID patients with a positive family
history aberrancies in the blood B cell compartment can be found also in
healthy family members. Since we expect that in more cases a familiar
background might be present, we also expect to find aberrancies in the B cell
compartment of family members of CVID patients where there is no positive
family history. We want to verify this by an in-depth analysis of the B cell
compartment. This in-depth analysis has been used to define CVID and other B
cell deficiencies.
Study objective
Investigation of the blood B cell compartment in family members of CVID
patients (with and without a CVID family history) to identify or exclude B-cell
defects and to improve our insight into a potential familial background of
CVID.
Study design
Pilot study to develop criteria for selection of families which have a higher
chance for a monogenetic versus a polygenetic background of CVID (see for more
information extensive description in the study protocol).
Study burden and risks
Only one time 9 mL of blood will be drawn from study participants. Since
drawing blood is common practice in a clinical setting, there are no additional
risks for participation of the study.
Philips van Leydenlaan 15
Nijmegen 6525EX
NL
Philips van Leydenlaan 15
Nijmegen 6525EX
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:;Inclusion criteria for the index case
- ESID-defined probable or possible CVID patients with or without positive family history for CVID according to the ESID registry (2014) criteria;Inclusion criteria for the family members
- Siblings (> 16 years of age), parents and grandparents
- Each participating family member will have to provide informed consent in order for the family to be eligible for inclusion.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- ESID-defined CVID patients having a known mono-genetic cause of CVID disease
- ESID-defined CVID patients having another mono-genetic disorder not obvious related to CVID
- ESID-defined CVID patients having a chromosomal defect
- Infections within 3 months prior to this study
- Surgeries within 6 months prior to this study
- Vaccinations within 3 months prior to this study
- Family members having significant disorders, including other immunodeficiency other than CVID, cancer, oral steroid therapy or any history of any comorbidity that, in the opinion of the investigator, might confound the results of the study
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 | NL69477.091.19 |