The main objective of this study is to investigate the migratory behaviour of neutrophils isolated from healthy individuals and gluten-related disease patients* blood to develop a diagnostic tool for gluten-related diseases that can replace biopsy…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Our primary goal is to confirm the differences in neutrophil migration
behaviour between control and celiac disease patients as observed in the
American study, for the Dutch situation, and to add non-celiac
glutensensitivity patients* neutrophils to the study in order to get insight in
both gluten-related diseases that allows us to develop a diagnostic kit based
on the obtained results. For this purpose we will set up the migration assay to
investigate neutrophils migration to gluten in these three study groups.
Secondary outcome
We intend to find a panel of biomarkers associated with the migration capacity
by performing RNA sequencing on isolated neutrophils from all three study
groups. RNA sequencing is an adequate and valid method to obtain important and
extensive information on the activation state of cells. This approach largely
increases the possibility to find shared values and differences between the
groups and allows us to get information that helps to understand underlying
mechanisms that are at the basis of the observed differences in neutrophil
migration behavior. Secondly, we will perform HLA-DQ2/DQ8 genotyping; since
virtually all celiac disease patients carry these haplotypes (>97%) it will be
important to determine these haplotypes in our participants in order to
properly define the study groups. We will measure celiac markers in serum at
time of assay as an essential check for the in-remission state of the disease
in celiac disease patients and to exclude celiac disease in our healthy control
group.
Background summary
Celiac disease is an autoimmune enteropathy triggered by gluten containing
cereals in genetically predisposed individuals. At immunological level, celiac
disease is characterized as a Th1/Th17-mediated autoimmune disease with high
mucosal titers of interferon-γ, and for this reason, throughout the years much
research effort has been put into studying the adaptive immune response. In
recent years, though, several studies showed involvement of the innate immunity
and hence provided new insight into our understanding of how gliadin triggers
inflammatory responses. Of particular interest for this application is the
observation that gluten appears a potent chemoattractant factor for
neutrophils. To what extent neutrophil function adds to, or protects against,
gluten intolerance still needs vigorous investigation. More recently, our
preliminary data revealed a distinct neutrophil migration behavior towards
gliadin in patients with celiac disease versus healthy controls in the United
States of America.
Study objective
The main objective of this study is to investigate the migratory behaviour of
neutrophils isolated from healthy individuals and gluten-related disease
patients* blood to develop a diagnostic tool for gluten-related diseases that
can replace biopsy and detect a gluten-associated disease even if the patient
is on a gluten-free diet. Our secondary objective is to find biomarkers
associated with neutrophil immune function by the determination of expression
levels of cell-specific immune mediators.
Study design
Neutrophils will be isolated from venous blood from healthy volunteers, celiac
and non-celiac gluten sensitive (NCGS) patient populations. One part of the
cells will be subjected to a migration assay and migration towards gluten will
be monitored. Another part of the cells will be used for measuring expression
levels of neutrophil immune activation and migration markers (for example:
receptors that fulfill their function in neutrophil migration). The data
together will complement each other and allow to get insight in neutrophil
migration and activation behavior in response to gluten.
Study burden and risks
Participating in this study does not lead to potential risks for the individual
participants. The only associated risk of participating in this study is the
blood draw procedure that may lead to a small transitory bruise, and dizziness
at the moment of blood sampling. This is a simple study in which we only
require a single-time blood sampling and completing a questionnaire; the amount
of time spent in the MUMC+ for this study approximately 30 minutes. No changes
in lifestyle habits will be requested.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
Age: 20-60 years old
Furthermore:
- Biopsy proven celiac disease patients in remission, on a strict gluten-free
diet since at least 3 months
OR
- Non-celiac gluten sensitive (NCGS) patients, reporting gastrointestinal or
extra-intestinal symptoms within 8 hours after gluten consumption, in whom
celiac disease has been ruled out by means of serology and/or biopsy, and on a
gluten-free diet since at least 3 months
OR
- Healthy volunteers without celiac disease or NCGS, who do not state any
symptoms after ingesting gluten
Exclusion criteria
- Gastrointestinal, genitourinary or immune diseases that can affect
interpretation of the results
- Pregnancy
- Use of antibiotics or immunosuppressive drugs within 90 days prior to the
study
- Excessive use of drugs or alcohol
- Participation in any other scientific study that may interfere with the
present 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
In other registers
| Register | ID |
|---|---|
| Other | Netherlands Trial Register (NTR) - nummer volgt |
| CCMO | NL74741.068.20 |
| OMON | NL-OMON29405 |