To determine whether nonspecific triggering of monocytes is associated with different epigenetic programming and expression of pro-inflammatory cytokines in clinically suspect arthralgia and in RA.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In case prolonged increased responsiveness of monocytes is one of the hits in
the multiple hit process of RA we anticipate that:
- There are differences in monocytes of RA patients and healthy controls.
- It is an early phenomenon, so it is already present in patients with
clinically suspect arthralgia with subclinical inflammation on the MRI.
These hypotheses will be tested in this study.
Secondary outcome
NA
Background summary
The development of rheumatoid arthritis (RA) is a multiple hit process and
patients with clinically suspect arthralgia and subclinical inflammation at the
MRI are at risk for RA development (this is studied in P. 11.210). Since the
development of RA is a multiple hit process, the challenge is to identify the
hits that are relevant for RA development.
The development of RA related auto-antibodies may be one of the hits; this
reflects a process that provides long term memory on the level of the adaptive
immune response. Other factors are presumably relevant as 40% of the
RA-patients are autoantibody negative.
Very recently it has been shown that the innate immune response is able to
display adaptive features as well. It has been shown that nonspecific
triggering of monocytes results in different epigenetic programming and
increased expression of pro-inflammatory that persists for at least three
months. This memory effect, which is called trained immunity, has been shown
relevant for increased responses to secondary infections. Our hypothesis is
that it also plays a role in the development of RA. In case prolonged increased
responsiveness of monocytes is one of the hits in the multiple hit process of
RA we anticipate that:
- There are differences in monocytes of RA patients and healthy controls
- It is an early phenomenon, so it is already present in patients with
clinically suspect arthralgia with subclinical inflammation on the MRI
Study objective
To determine whether nonspecific triggering of monocytes is associated with
different epigenetic programming and expression of pro-inflammatory cytokines
in clinically suspect arthralgia and in RA.
Study design
This explorative study has a cross-sectional design and evaluates monocytes
derived from PBMCs of 20 healthy persons, 20 patients with clinically suspect
arthralgia and subclinical inflammation on the MRI and 20 RA patients. The
clinically suspect arthralgia (CSA) patients are included in the study
*identifying rheumatoid arthritis in a preclinical phase*( P11.210).
Since in general both RA and CSA patients are middle aged and have a
female:male ratio of 2:1, the healthy controls will be matched for age and
gender to the patient groups.
Study burden and risks
NA
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
patients with clinically suspect arthralgia and inflammation on the MRI
patients diagnosed with RA
healthy volunteers
aged >=18 years
all subjects have to give their written informed consent.
Exclusion criteria
not fulfilling inclusioncriteria
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 | NL49496.058.14 |