1) To investigate IFN type I signature as an early biomarker for progression to SLE. 2) To establish effects of increased innate immune system activation on adaptive immune system, in particular on B-cells. 3) To establish IFN type I activation as…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main parameter is expression of IFN type I signature
Secondary outcome
- Other parameters of increased innate immune system activation will be
measured including levels of MxA in monocytes and serum, TLR protein expression
by FACS and TLR mRNA expression by RT-PCR, and serological biomarkers (a.o. TNF
alpha, IL-6 and CXCL-10) will be assessed with luminex
- As marker of inflammation and apoptosis, levels of HMGB-1 will be determined.
- Production of different auto-antibodies (IgG, IgA and IgM)will be measured
and comprise ANA (titer and pattern), ENA, anti-dsDNA antibodies,
anti-phospholipid antibodies and anti-HMGB1 antibodies. Furthermore, levels of
BAFF and APRIL will be determined by luminex. Also, the distribution of B cell
subsets by FACS analysis with focus on autoreactive effector memory cells will
be assessed.
- To investigate the influence of the innate immune system on B cell
activation, B cells will be activated in vitro with TLR agonists to investigate
ability to produce inflammatory proteins.
- To establish IFN type I activation as biomarker of progression to SLE in skin
biopsies. At inclusion, in all ILE patients skin biopsies will be taken of
unaffected skin and if present of affected skin. Next to IFN type 1 activation,
markers for apoptosis and TLR expression will be measured, both at protein and
mRNA level.
- To investigate the effects of HCQ, all biomarkers mentioned above will be
assessed including skin biopsies, before and after 16 weeks of treatment with
HCQ, which will be prescribed on clinical grounds.
Background summary
Systemic lupus erythematosus (SLE) is a complex disease characterized by a
broad spectrum of clinical manifestations and a multitude of laboratory
abnormalities. However, knowledge is lacking about the earlier phases of the
disease, also called Incomplete Lupus Erythematosus (ILE). Also, not all ILE
patients will develop SLE. At this moment no biomarkers are known to predict
which of these individuals will progress to SLE. We hypothesize that ILE
patients who are prone to progress to SLE, will have an increased activation of
the innate immune system, characterized by increased type I interferons (IFNs)
and Toll Like Receptors (TLRs) expression, leading to increased B cell
activation. These changes might be present systemically in the blood as well as
in the skin. We postulate that hydroxychloroquine (HCQ) modulates these
pathologic differences, as this drug modulates TLR activation.
Study objective
1) To investigate IFN type I signature as an early biomarker for progression to
SLE. 2) To establish effects of increased innate immune system activation on
adaptive immune system, in particular on B-cells. 3) To establish IFN type I
activation as biomarker of progression to SLE in skin biopsies. 4) To
investigate the effects of HCQ in a selected group of ILE patients, in whom HCQ
is prescribed for clinical reasons.
Study design
This will be a longitudinal follow up study in ILE patients. At baseline
clinical data and several markers for innate immune activation and B cell
activation will be determined. The same analyses will be done in matched SLE
patients and healthy controls. Furthermore, at inclusion in all ILE patients
skin biopsies will be taken of unaffected skin and if present of affected skin.
All ILE patients will be followed during regularly visits to our out-patient
clinic (every 3-6 months). At each visit blood will be drawn for biochemical
and immunological investigation and clinical data will be collected.
Progression to SLE will be recorded. In a subgroup of newly diagnosed ILE
patients, the effects of HCQ on innate immune system activation and B cell
activation will be measured on t = 0 and t = 16 weeks.
Study burden and risks
All patients will receive standard diagnostic workup, treatment and follow up.
Procedures that will be solely done for study purposes are: extra blood
withdrawal and at entry of the study two or four skin biopsies. When patients
participate in the part of the study concerning effects of HCQ, one extra visit
to the hospital is required. Healthy controls will be seen by one of the
rheumatologists for determining whether they are healthy to serve as controls,
and then blood will be drawn during the same visit.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
Incomplete Lupus patients:
- ANA positivity with a titre of at least 1:80 or higher
- Two other ACR criteria of SLE
- Disease duration of < 5 years
- (Preferable) not yet treated with hydroxychloroquine or corticosteroids
- Being able to give informed consent
Exclusion criteria
- Concomitant chronic diseases that may affect immune system (such as prior or current malignant disease, active infectious disease, other rheumatological disease, kidney disease, active allergy etc.)
- Pregnancy
- < 18 years old
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 | NL54268.042.15 |