The in vivo mechanisms that control migration of pathogenic dermal T-cells to synovial joints during psoriatic arthritis: the role of dermal lymphatic vessels.
- Conditions
- ie. chronic skin inflammation with joint inflammationpsoriasis and psoriatic arthritis100038161002321310014982
- Registration Number
- NL-OMON47603
- Lead Sponsor
- Maasstadziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 101
Inclusion criteria psoriasis patients:
- patients that are diagnosed with psoriasis by their dermatologist
- age * 18 years
- written informed consent by the patient;Inclusion criteria psoriatic arthritis patients:
- Psoriasis patients that are diagnosed with psoriatic arthritis by their rheumatologist (according
to the CASPAR criteria)
- age * 18 years
- written informed consent by the patient;Inclusion criteria healthy volunteer:
- age * 18 years
- WHO performance score 0
- age and sex matched (for psoriasis and psoriatic arthritis)
- written informed consent ;Inclusion criteria systemic sclerosis patients:
- Patients that are diagnosed with systemic sclerosis by their rheumatologist
- age * 18 years
- written informed consent given by the patient;Inclusion criteria systemic lupus erythematodes patients:
- Patients that are diagnosed with systemic lupus erythematodes by their rheumatologist
- age * 18 years
- written informed consent given by the patient;Inclusion criteria vasculitis patients with skin involvement:
- Patients that are diagnosed with vasculitis by their rheumatologist
- age * 18 years
- written informed consent given by the patient;Human tissues;Inclusion criteria for tissue donors, ie. skin tissue: patients undergoing eyelid surgery; mammareduction/abdominoplasty; synovial tissue: knee-replacement therapy in PsA and osteoarthritis (orthopedic surgery), synovectomy wrist (plastic surgery)
- donors will be asked for their permission to use their materials anonymously; this will be recorded in their medical file.;Inclusion criteria for tissue donors, ie. patients undergoing vascular surgery. The 3 categories of vascular surgery patients that will be included are patients undergoing crossectomy in chronic venous insufficiency; carotid endarterectomy, and surgical bypass of aortoiliac occlusive disease in patients with intermittent claudicatio without any signs of infection or critical (limb) ischemia.
- written informed consent given by the patient
- use of corticosteroids including topical or systemic for the last 6 weeks
- use of disease-modifying antirheumatic drugs (DMARDs) or immune-suppressive drugs
for the last 6 weeks
- concomitant use of drugs affecting the lymphatic system and/or immune responses
including non-steroidal anti-inflammatory drugs (NSAIDs), drugs targeting RAAS system,
and anti-allergy medication. These agents must be discontinued at least 6 weeks before
the screening visit.
- co-existence of chronic inflammatory disorders including eczema, asthma or chronic
infection
- pregnancy
- active cancer
- any lymphatic, cardiovascular or immunodeficiency disorder
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Objective 1.<br /><br>Study parameter: To establish that skin-derived and synovium-derived LECs in<br /><br>PsA drive the in vivo mechanisms that coordinate the programming of dermal<br /><br>pathogenic T-cells to adopt a synovial joint homing profile, ie. enhanced<br /><br>expression of CD161, CCR6, CCR7, CCR2, CXCR6, and loss of skin homing receptors<br /><br>such as CCR4, CCR10 and CLA(based on recent literature)<br /><br><br /><br><br /><br>Outcome<br /><br>Expected results In these experiments, we expect to find that dermal LECs from<br /><br>PsA patients (in contrast to PsO and controls) are capable of imprinting<br /><br>skin-derived T-cells with a synovial joint homing phenotype that promote their<br /><br>egress towards synovial joint compartments. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Objective 2. To investigate whether the induction of tissue-imprinting<br /><br>receptors on allogenic skin-derived T-cells, as demonstrated in Aim 1, leads to<br /><br>enhanced T-cell migration into the afferent lymphatic vessels of a human dermal<br /><br>sheet (crawl-in assay).<br /><br><br /><br>Outcome:<br /><br>Should an effect of PsA-induced inflammatory changes in LECs on the homing<br /><br>profile of these skin-derived T-cells be confirmed, this will most likely have<br /><br>a direct impact on the T-cell migratory response as reflected by an increased<br /><br>entry into afferent lymphatics in the crawl-in assay.<br /><br><br /><br>Objective 3. To investigate whether overlapping properties may be present in<br /><br>LECs from the skin, synovial tissue and lymph nodes.</p><br>