Our aim of the study is to investigate IL-7, TSLP and CD30(L) expression in SLE patients en healthy controls to better understand pathogenesis and to find a biomarker that is related to disease activity. With this potential new therapeutic targets…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The expression of IL-7, TSLP, CD30L and their receptors in peripheral blood and
urine of patients with SLE as compared to healthy controls.
Secondary outcome
The longitudinal approach will be used to assess the correlation between the
changes in IL-7, TSLP and CD30L and their receptor with the changes in disease
activity and immunologic parameters.
Identify biomarkers different from healthy controls that reflect disease
activity and can be play a role in the pathogenesis of SLE. The results of the
proposed studies may contribute to a future treatment strategy by blockade of
some of the investigated inflammatory mediators.
Third objective: Leucocytes will also be stored for DNA isolation, which will
be used for analyses of polymorphic sites that might be involved in regulation
of transcription of the investigated molecules
Background summary
Systemic lupus erythematosus (SLE) is an auto-immune disease in which the
interplay between dendritic cells and T and B cells plays an important role in
the immunopathology. IL-7 and IL-7-related cytokine TSLP (thymic stromal
lymphopoeitin) are members of the IL-2 family that are able to promote
autoimmunity by activation effector T cells and dendritic cells. Activated T
cells cause activation of B cells by upregulated expression of costimulatory
molecules such as CD30L. This latter molecule is crucially involved in the
generation of pathogenic autoantibodies in animal models for SLE.
Despite all this we do not completely understand the pathogenesis of this
disease. In relation with that, a biomarker found in pathogenesis that
correlates with disease activity is still lacking
Study objective
Our aim of the study is to investigate IL-7, TSLP and CD30(L) expression in SLE
patients en healthy controls to better understand pathogenesis and to find a
biomarker that is related to disease activity. With this potential new
therapeutic targets can be developed.
Study design
It*s a prospective observational cohort study of SLE-patients, with
longitudinal and cross-sectional analysis.
After providing informed consent, clinical data will be gathered including
information regarding previous history of lupus activity and involvement, past
concomitant medical diseases, past medical history, concomitant medications and
a disease acitivty measurement (SLEDAI and BILAG). Additionally 80cc*s of blood
will be sampled from which serum and cells for DNA and Phosflow will be
isolated and from which miRNA and mRNA will be isolated from the T-cell,
monocyte and remaining cell-populations. After that flow-cytometry data from
whole blood will be provided to Amgen.
Clinical data, urine collection and sampled blood will be five times in 1 year
(timepoint 0, 3, 6, 9 and-12 months) in the active patients (n=20). For the
inactive patients clinical data en blood en urine will be sampled only once. In
case of active disease during follow-up, these patients will be followed every
3 months with samples en clinical data at entry (inactive), active fase, 3
months, 6 months and 12 months (somewhat like the active patients at inclusion).
The same biomaterials will be collected from 25 healthy controls at five
timepoints for 10 persons en only once for 13 persons
Study burden and risks
There will be no additional risks for the subject. Blood is already taken three
monthly in the standard follow-up of SLE patients. Now there will be taken
extra blood (80cc) for research in the same setting, so basically no extra
venapuncture is needed in the patient group. The healthy controles need a
venapuncture but the underlying risks can be neglected. No other invasive
procedures will be done.
Heidelberglaan 100
3584CX Utrecht
NL
Heidelberglaan 100
3584CX Utrecht
NL
Listed location countries
Age
Inclusion criteria
Patients full-filling the ACR criteria for systemic lupus erythematosus
Controles: 18 years or older
Exclusion criteria
Patients: patients with proven other auto-immune disorders, pregnancy and malignancy
Controls: a history or presence of auto-immune disease and current use of immunosupressants or pregnancy
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 | NL34374.041.11 |