In this study, therefore, we aim to investigate how trained immunity is systemically regulated in SLE patients and how the degree of trained immunity affects disease activity and severity. A better understanding of these processes contributes to the…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. What are the differences in the transcriptome of circulating monocytes from
SLE patients when the disease is in remission or when the disease is active
(flares), and how does this differ with the transcriptome of circulating
monocytes from healthy individuals?
2. What are the differences in the epigenome of circulating monocytes from SLE
patients when the disease is in remission or when the disease is active
(flares), and how does this differ with the epigenome of circulating monocytes
from healthy individuals?
3. What are the differences in the cytokine response of circulating monocytes
from SLE patients when the disease is in remission or when the disease is
active (flares), and how does this differ with the response of circulating
monocytes from healthy individuals?
Secondary outcome
1. Are there correlations between the trained immunity profile of circulating
monocytes (identified by transcriptome, epigenetics, and cytokine response) and
the degree of current disease activity in clinical variables of SLE patients?
2. Are there correlations between the trained immunity profile of circulating
monocytes (identified on the basis of the transcriptome, epigenetics, and
cytokine response) and the risk of the occurrence of flares in the future.
3. Are there correlations between the trained immunity profile of circulating
monocytes (identified based on the transcriptome, epigenetics, and cytokine
response) and inflammatory markers in the blood.
Background summary
Systemic lupus erythematodes is an autoimmune disease that can affect several
organs, including the kidney. Many patients develop lupus nephritis, which can
result in kidney failure. For this group of patients, dialysis or a kidney
transplant is the only option. Patients with SLE are treated with
immunosuppressive medications, including hydroxychloroquine, corticosteroids,
mycophenolate mofetil and cyclophosphamide. However, these medications inhibit
the immune system aspecifically and can have serious side effects.
The reason why SLE develops in some people is unclear, nor is there yet a good
SLE-specific treatment. SLE is characterized by dysfunction in processing dead
(apoptotic) cellular material and loss of immunological tolerance to nuclear
antigens. The main source of these extracellular antigens are apoptotic
microparticles (MP) and "neutrophil extracellular traps" (NETs).
Studies on the immunological mechanisms leading to SLE are mainly focused on
the adaptive immune system, because T and B cells play an important role in
antibody formation against nuclear antigens, which is characteristic of SLE.
However, cells of the nonspecific immune system (monocytes, macrophages and
dendritic cells) also play an important role in SLE although less research has
been done on these. These cells are activated by MPs and NETs. Previous
observations have shown that these cells in SLE patients are much more
sensitive to activation by MPs and NETs compared with cells from healthy
individuals. In addition, these cells have been shown to be much more active in
SLE patients than in healthy individuals. The activation of these cells
contributes significantly to the tissue damage that occurs when there is
disease activity from SLE (a "flare").
In this study, we are investigating trained immunity in SLE patients. Trained
immunity is a form of memory of innate immune cells, which causes increased
inflammatory activity upon stimulation. Our hypothesis is that trained immunity
may lead to activation of the immune response in SLE patients and contribute to
the disease flare.
Study objective
In this study, therefore, we aim to investigate how trained immunity is
systemically regulated in SLE patients and how the degree of trained immunity
affects disease activity and severity. A better understanding of these
processes contributes to the discovery of new targets for therapy for SLE
patients.
Study design
This is a clinical observational study.
Study burden and risks
This is an observational study in which participants complete a questionnaire,
have their blood pressure measured and donate body fluids (urine and blood), ln
our view, there are no risks associated with this. The burden for participation
in this study is minimal and consists of a 1-hour visit to our outpatient
clinic.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
Age between 18 and 70 years old.
Positive SLE diagnosis.
Exclusion criteria
Lack of informed consent
Current infection
CKD stage 5 or dialysis
Pregnancy
Active cancer
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 | NL84023.091.23 |