1. To examine whether the PI3K-AKT pathway is overly activated in children with Down syndrome compared to healthy age-matched controls. 2. To determine the rate of exhaustion and the apoptosis of lymphocytes in children with DS. 3. To determine the…
ID
Source
Brief title
Condition
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Deregulated AKT phosphorylation assays in both groups.
Secondary outcome
B- and T-cell subset abnormalities, rate of apoptosis, exhaustion present in
lymphocytes and immunoglobulines.
Background summary
Down syndrome (DS) is associated with a higher prevalence of auto-immune
diseases and infections. Moreover, severe respiratory tract infections are one
of the major causes of death in individuals with DS. Detailed knowledge of the
impaired immune system in DS and its contribution to the susceptibility to
infections is scarce. Patients with activated PI3K-* syndrome (APDS) have an
immunological phenotype and clinical presentation resembling to patients with
DS. The mechanism responsible for APDS is the over-activation of the
PI3K-AKT-pathway, which was also activated in one of our own patients with DS.
Also, research comparing healthy adults with individuals with DS showed
hyperactivation of this pathway in the frontal cortex in DS. Therefore, we
hypothesize that the altered immune system of children with DS can be partially
explained by an increased activity of the PI3K-AKT pathway, enhancing the risk
to suffer from infections such as severe respiratory tract infections (RTIs).
Study objective
1. To examine whether the PI3K-AKT pathway is overly activated in children with
Down syndrome compared to healthy age-matched controls. 2. To determine the
rate of exhaustion and the apoptosis of lymphocytes in children with DS. 3. To
determine the association between the AKT-pathway and the degree of antibody
deficiency and clinical symptoms in children with DS.
Study design
Observational non-interventional cohort study with a cross-sectional design
comparing the immunological characteristics of children with DS with healthy
age matched children (n=42). The study results will be compared to data from
APDS patients as a model of proven PI3K-AKT over-activation.
Study burden and risks
Clinical data will be collected during regular clinical follow up visits. The
(extra) blood sample will be collected when blood gets drawn for regular
healthcare purposes. In the control group, samples will be collected from the
peripheral intravenous catheter which is placed for clinical reasons (minor
surgery). There is no extra risk for the child because it will not result in an
extra intervention. Only minors will be included in the study, as the onset of
infections is predominantly present in childhood. This study does not directly
benefit patients with Down syndrome and healthy controls. If our hypothesis
proves to be correct the AKT-pathway eventually might serve as a therapeutic
target to reduce morbidity and mortality among patients with Down syndrome.
Els Borst-Eilersplein 275
Den Haag 2545 AA
NL
Els Borst-Eilersplein 275
Den Haag 2545 AA
NL
Listed location countries
Age
Inclusion criteria
- Age 1 month-18 years;
- For subjects with Down syndrome: diagnosis by chromosomal analysis;
- For healthy age-matched controls: undergoing a minor surgical procedure;
- Weight >5 kg;
- Informed consent from parent(s)/caregiver(s) with legal custody and/or the subject (according to the WGBO).
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Any active infectious disease (viral or bacterial), excluding mild upper respiratory tract infections without fever;
- Any type of malignancies, including lymphoproliferative disease (except of squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence);
- Mosaic Down Syndrome;
- Current treatment with prophylactic antibiotics, monoclonal antibodies or immunosuppressant*s;
- Auto-immune diseases other than those associated with Down Syndrome;
- For healthy individuals: known with recurrent respiratory tract infections (RRTIs) and/or getting ear, nose or throat (ENT) surgery because of this reason.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | NL63464.098.17 |