The primary objective is to determine whether the DC/B-cell response to C. jejuni LOS differs in (ex-)patients with C. jejuni-related GBS compared to healthy controls. Secondly, we aim to define the variation in DC/B-cell response to C. jejuni LOS…
ID
Source
Brief title
Condition
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The DC response to LOS as determined by: 1) B-cell proliferative capacity; 2)
production of cytokines, including interferon (IFN)-β, interleukin (IL)-6,
IL-10, IL-12 and tumor necrosis factor (TNF)-α; and 3) expression of
differentiation markers, including CD40, CD80, CD86 and HLA-DR.
Secondary outcome
Gene expression profile of DC stimulated with C. jejuni LOS of (ex-)GBS
patients and healthy controls.
Background summary
Campylobacter jejuni is the predominant preceding infection in Guillain-Barré
syndrome (GBS) and is associated with severe weakness and poor prognosis.
Molecular mimicry between C. jejuni lipo-oligosaccharides (LOS) and
gangliosides induces cross-reactive antibody responses precipitating peripheral
nerve damage. This aberrant immune response after C. jejuni infection only
occurs in a minority of susceptible persons. Dendritic cells (DC) are known to
orchestrate the immune response to infection. In recent pilot studies we found
that DC and B-cell responses to C. jejuni LOS differ significantly between
persons. High responders may be at risk to develop GBS after C. jejuni
infection. We hypothesize that the DC and B-cell response to C. jejuni LOS
defines the constitutional susceptibility to develop GBS after C. jejuni
infection.
Study objective
The primary objective is to determine whether the DC/B-cell response to C.
jejuni LOS differs in (ex-)patients with C. jejuni-related GBS compared to
healthy controls. Secondly, we aim to define the variation in DC/B-cell
response to C. jejuni LOS in healthy controls. Finally, using gene expression
profiles we will define the crucial DC molecules that determine a high
DC/B-cell response to C. jejuni LOS.
Study design
Cross-sectional observational cohort study and longitudinal observational
cohort study
Study burden and risks
Subjects will be asked to visit the Outpatient clinic neurology. Blood will be
drawn to isolate white blood cells and to isolate DNA. These samples will be
obtained in less than 10 minutes and carry negligible risks.
The identification of host factors that cause GBS will be of benefit to future
patients, since persons could be identified with a high risk of developing GBS
after C. jejuni infection. This is important for epidemiological studies in GBS
and for excluding persons in vaccination studies for C. jejuni. In addition,
understanding the activation of DC by C. jejuni may provide a rationale to
develop new treatments that interfere with the early immune response,
preventing the subsequent activation of B cells. This approach will add to
current therapeutic strategies that target the effector phase of the disease,
such as IVIg, plasmapheresis and complement inhibitors.
Dr Molewaterplein 50
3015 GE Rotterdam
NL
Dr Molewaterplein 50
3015 GE Rotterdam
NL
Listed location countries
Age
Inclusion criteria
Healthy controls (partners, non-related family members or friends of the (ex)-GBS patients):
- Age 18 years or older
- Written informed consent given by the subject.
Ex-GBS patients:
- Fulfilling the diagnostic criteria for GBS (Asbury, 1990)
- Culture-proven and/or positive serology for C. jejuni (at time of diagnosis).
- Current age: 18 years or older
- Diagnosis of GBS was made after 1987 and at least one year before inclusion in the study.
- Patients were treated at the ward of the department of Neurology, Erasmus MC, or at the Sophia Children*s Hospital.
- Written informed consent was given by the subject.
Exclusion criteria
Both groups:
- Additional diseases or disorders at the time of diagnosis or at time of blood sampling that may influence the endpoints:
*autoimmune diseases (like multiple sclerosis, psoriasis, Crohn*s disease, ulcerative colitis, hepatitis, rheumatoid arthritis, SLE and other systemic diseases)
*acute and chronic infectious diseases (like infectious mononucleosis, HIV/AIDS)
*malignancies (not in remission);- Medicines at time of blood sampling that may affect endpoints (i.e. inflammatory processes):
*NSAIDs, corticosteroids, cyclosporine
*Cytostatic compounds
*Cytokines (analogues) and biologicals
*Intravenous immunoglobulins.
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 | NL33335.078.10 |