Recirculating Memory T Cells in the Pathogenesis of Psoriatic Arthritis and Cutaneous Psoriasis

• ClinicalTrials.gov Identifier: NCT03374527
• Recruitment Status: Completed
• First Posted: December 15, 2017
• Last Update Posted: September 9, 2019
• Sponsor: Istituto Ortopedico Galeazzi
• Information provided by (Responsible Party): Istituto Ortopedico Galeazzi

Study Description

Brief Summary:

The aim of the study is to investigate the link between pro-inflammatory T cells responses arising in the skin in patients with cutaneous psoriasis and those present in the joints of patients developing psoriatic arthritis.

The study is based on the hypothesis that a fraction of T cells with memory phenotype can recirculate from the skin and relocalize at extracutaneous sites including enthesis or synovial tissue thus propagating the pro-inflammatory cycle. This could represent a pathogenic mechanism in the development of PsA.

The main aim of the study is to define the phenotypic and functional differences of circulating T cells in patients cutaneous psoriasis, patients with psoriatic arthritis and in control group of healthy subject.

To this end the investigators analyze the expression of cell surface markers of central memory (TCM), effector memory (TEM) and effector (Teff) cells, within this subsets the investigators evaluate the expression of chemokine receptors as well as skin and tissue homing molecules. There will be also an evaluation of the T cell polarization towards Th1/Tc1 or Th17/Tc17 phenotype by evaluating the cytokine expression profile.

In selected patients with PsA the researchers analyze in parallel the phenotype and the cytokine profile of T cell subpopulations in peripheral blood and in synovial fluid, The results of this study could possibly allow to define distinctive features of circulating T cells in patients with PsA and to understand the link between circulating and synovial fluid T cells in patients with PsA.

Condition or disease	Intervention/treatment
Psoriasis; Psoriatic Arthritis	Other: blood sample collection; Procedure: Synovial Fluid collection

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 110 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Target Follow-Up Duration: 1 Day
• Official Title: Recirculating Memory T Cells in the Pathogenesis of Psoriatic Arthritis and Cutaneous Psoriasis
• Actual Study Start Date: October 16, 2014
• Actual Primary Completion Date: January 30, 2018
• Actual Study Completion Date: June 13, 2018

Groups and Cohorts

Group/Cohort	Intervention/treatment
Psoriasis; Patients with psoriasis vulgarism without clinical signs of PsA	Other: blood sample collection; Blood samples are collected from patients with psoriasis vulgaris and patients with psoriatic arthritis following the routine procedure. Blood samples will also be collected from healthy control subjects.
Psoriatic Arthritis (PsA); Patients with a diagnosis of psoriatic arthritis and cutaneous psoriasis	Other: blood sample collection; Blood samples are collected from patients with psoriasis vulgaris and patients with psoriatic arthritis following the routine procedure. Blood samples will also be collected from healthy control subjects.; Procedure: Synovial Fluid collection; Synovial fluid is collected when prescribed in patients with psoriatic arthritis
Control group; Healthy subjects	Other: blood sample collection; Blood samples are collected from patients with psoriasis vulgaris and patients with psoriatic arthritis following the routine procedure. Blood samples will also be collected from healthy control subjects.

Outcome Measures

Primary Outcome Measures :

1. Evaluation of the percentage of different subsets of memory T cells in the circulation of patients with psoriasis, patients with psoriatic arthritis and a control group of healthy subject. [ Time Frame: At time of blood collection ]
   Central memory, Effector memory and Effector cell markers are evaluated in circulating CD4 and CD8 T cells. Within these subsets the expression of chemokine receptors is also evaluated and we define the cytokine secretion profile for each subset.

Secondary Outcome Measures :

1. Correlation between the circulating percentage of individual subsets of CD4 and CD8 T cells and the clinical disease parameters: Psoriasis Area and Severity Index (PASI) Score and serum level of C reactive protein (CRP) [ Time Frame: At time of blood collection ]
   For each subsets it is calculated the correlation between the percentage in the circulation and either the Psoriasis Area and Severity Index (PASI) score or the serum level of C reactive protein
2. Parallel analysis of the phenotype of CD4 and CD8 T cells in the circulation and in synovial fluid of patients with psoriatic arthritis. [ Time Frame: At time of blood and synovial fluid collection ]
   Phenotype and functional analysis of T Cells

Biospecimen Retention:   Samples Without DNA

Peripheral blood mononuclear cells, blood serum, synovial fluid mononuclear cells, synovial fluid

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Cohort

Criteria

Inclusion Criteria:

• Patients with a diagnosis of cutaneous psoriasis without clinical signs of PsA,
• Patients with a diagnosis of PsA
• Healthy subjects with a negative family and personal anamnesis for psoriasis.
• Absence of acute and chronic systemic or cutaneous infections during sample collections.

Exclusion Criteria:

• Treatment with cyclosporin A, methotrexate, systemic corticosteroids or any other immunosuppressant agent within 3 weeks before the blood samples collections.

Contacts and Locations

Locations

Italy

IRCCS Galeazzi Orthopedic Hospital

Milan, Italy, 20161

Sponsors and Collaborators

Istituto Ortopedico Galeazzi

Investigators

• Principal Investigator: Eva Reali, Dr.; Istituto Ortopedico Galeazzi

More Information

Additional Information:

Publications of Results:

Diani M, Galasso M, Cozzi C, Sgambelluri F, Altomare A, Cigni C, Frigerio E, Drago L, Volinia S, Granucci F, Altomare G, Reali E. Blood to skin recirculation of CD4(+) memory T cells associates with cutaneous and systemic manifestations of psoriatic disease. Clin Immunol. 2017 Jul;180:84-94. doi: 10.1016/j.clim.2017.04.001. Epub 2017 Apr 6.

Sgambelluri F, Diani M, Altomare A, Frigerio E, Drago L, Granucci F, Banfi G, Altomare G, Reali E. A role for CCR5(+)CD4 T cells in cutaneous psoriasis and for CD103(+) CCR4(+) CD8 Teff cells in the associated systemic inflammation. J Autoimmun. 2016 Jun;70:80-90. doi: 10.1016/j.jaut.2016.03.019. Epub 2016 Apr 8.

• Responsible Party: Istituto Ortopedico Galeazzi
• ClinicalTrials.gov Identifier: NCT03374527 History of Changes
• Other Study ID Numbers: T-ART
• First Posted: December 15, 2017
• Last Update Posted: September 9, 2019
• Last Verified: August 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Istituto Ortopedico Galeazzi:

T-cells; circulation; synovial fluid; psoriasis; psoriatic arthritis

Additional relevant MeSH terms:

Arthritis; Arthritis, Psoriatic; Psoriasis; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Skin Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases