1. To identify immunological alterations in peripheral lymphoid/skin/synovial tissue of patients with psoriatic artritis and psoriasis2. To correlate these alterations with disease stage, prognosis, treatment response3. To compare immunological…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
- Cornification and dystrophic skin disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Frequencies and phenotype of immune cell populations in peripheral lymph
nodes (inguinal LNs), skin and joint tissues in psoriatic artritis and
psoriasis
2. Differences in immune cell populations profiles (cytokine production,
genetic, epigenetic and transcriptional alterations) in peripheral lymph nodes,
skin and joint tissues psoriatic artritis and psoriasis
Secondary outcome
1. Frequency and gene expression profiles of stromal cells in lymph nodes of
psoriatic artritis and psoriasis patients
2. Frequency and phenotype of immune cells in psoriatic plaque lesions, lymph
node and inflamed synovial tissue
3. Gene expression profiles in skin/synovial tissue/lymph node tissue in
psoriatic artritis and psoriasis patients
Background summary
One of the biggest barriers to progress towards better treatment outcomes in
psoriatic arthritis (PsA) is 1) the lack of understanding of the disease
etiology and mechanisms involved, 2) and the lack of biomarkers that could help
in early (preclinical) diagnosis of the disease. The peripheral lymph nodes
(LN) are lymphoid structures that are involved in shaping peripheral immunity.
So far it is unknown whether and how these lymphoid structures are involved in
PsA pathogenesis, especially in the transition from psoriasis (PsO) to PsA. We
hypothesize that peripheral lymphoid tissues are involved in PsA
pathophysiology and the lymph nodes display an activation state of immune and
stromal cells which plays an important role in the transition from PsO to PsA.
We aim to investigate the involvement of the peripheral lymphoid tissue in the
immune deregulation that is observed in PsA and PsO patients and compare these
to other target tissues such as skin and synovial tissue.
Study objective
1. To identify immunological alterations in peripheral lymphoid/skin/synovial
tissue of patients with psoriatic artritis and psoriasis
2. To correlate these alterations with disease stage, prognosis, treatment
response
3. To compare immunological alterations in the lymphoid tissues to
immunological alterations in psoriatic skin and synovial tissue
The specific types of immunological alterations that we will study include:
• Phenotype and function of T and B cells and innate immune cells
• Cytokine production by innate immune cells and stromal cells
• Genetic, epigenetic and transcriptional alterations of immune cells and
stromal cells
• TCR repertoire
• Signaling events in immune cells and stromal cells
• Immunomodulation using stromal cells and/or other cells with regulatory
properties
Study design
An investigator initiated cross-sectional study for immune cell
characterization and gene expression analysis in skin, lymph node and joint
tissues in psoriatic artritis and psoriasis patients.
Study burden and risks
Inguinal lymph node biopsy sampling is well-tolerated. The technology was
established at the AMC>10 years ago and has since become a common research tool
in rheumatology patients. Inguinal lymph node biopsy is an outpatient procedure
which is performed under local anaesthesia and is well tolerated. Skin biopsy
is an procedure performed under local anesthesia on regular basis in the
dermatology outpatient clinics and is well tolerated. Blood sampling will be
conducted in the framework of the routine tests of the patients. Synovial fluid
and synovial tissue will be collected from PsA patients with manifested knee,
wrist or ankle joint arthritis or from PsO patients presenting with knee,
wrist, MCP-joint or ankle joint arthritis during follow-up. Skin biopsies will
be collected from PsO patients with at least one psoriatic plaque skin lesion.
Biopsies of skin and lymph node will be repeated in psoriasis and psoriatic
artritis patients undergoing therapy with conventional or biological DMARDs,
before start of treatment and around minimal four weeks after start of
treatment.
Meibergdreef 9
Amsterdam 1100DD
NL
Meibergdreef 9
Amsterdam 1100DD
NL
Listed location countries
Age
Inclusion criteria
All patients 18 years or older with a clinical diagnosis of PsO or PsA
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study: • Patients, who are not able to provide
informed consent. • History of malignancy • Viral or bacterial infection within
the past 4 weeks • Patients using anticoagulant therapy • Present or previous
use of systemic corticosteroids less than 28 days before enrollment • Present
or previous treatment with any cell depleting therapies, including
investigational agents. • Presence of any disease for which study subjects need
chronic or intermittent immunosuppressive therapy (e.g. prednisolone). •
History of chronic viral infection • Recent (<1 week) bacterial or viral
infection • History of autoimmune disease • Recent (< 4 weeks) vaccination
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 | NL82026.018.22 |