CD73+ Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis

NCT ID: NCT03953378

Last Updated: 2019-05-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 41 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2018-12-31

Brief Summary

Prospective study to investigate the correlation between CD39/CD73 expression by the different T lymphocyte subpopulations in the blood and synovial fluid (if available) into patients with chronic inflammatory rheumatism RA and PsA types, with the rheumatic activity, the background therapy (with Methotrexate (MTX)) and the response to this treatment.

Detailed Description

Th1.17 compose a recently described subset of highly polyfunctional and thus potentially more harmful CD4+ effector T cells (Teff) than classical Th17 as they co-produce interferon-γ (IFN-γ) and interleukin-17A (IL-17A). For this reason, Th1.17 rise increasing interest in RA and PsA since they seem involved in their pathophysiology. Hyper activation of Teff in RA and PsA results partly from a deficiency in regulatory mechanisms of Teff's pro-inflammatory functions. The ecto-nucleotidase CD73 delineates Teff enriched in Th1.17 features and acts as a regulatory mechanism for these pro-inflammatory cells. Considering that MTX, usually used as first line treatment of RA and PsA, increases extracellular concentrations of adenosine monophasphate (AMP) and immunosuppressive adenosine, the investigators hypothesized that CD4+CD73+ T cell effector population enriched in Th1.17 and Th17 cells may participate in the pathogenicity of RA and PsA but also in the resistance to MTX treatment through the specific expression of CD73 essential for Ado generation and which is down-regulated on proliferating T cells.

Conditions

Rheumatoid Arthritis; Psoriatic Arthritis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Group "RA patients"

Patients with Rheumatoid Arthritis (RA) fulfilling the American College of Rheumatology and European League Against Rheumatism 2009 criteria.

Multi-parametric Flow Cytometry analysis on patients and healthy donors samples

Intervention Type: OTHER

Collection of venous blood (16 mL) and synovial fluid (when available) samples, for each patient, at inclusion and in the frame of the usual medical follow-up at 3 months and between 6 and 12 months, before the onset of MTX (untreated patients) or during the course of MTX treatment (MTX-treated patients).

Collection of anonymous healthy donors blood samples, age- and sex-matched, obtained from the Etablissement Français du Sang.

Multi-parametric Flow Cytometry analysis was performed on these samples to assess CD73 expression on total memory T cells and within T helper lymphocyte subsets, their cytokine production and AMPase functions. For FoxP3 intracellular staining, cells were treated using the FoxP3 Fixation and Permeabilization kit (Life Technologies), according to manufacturer instructions. Stainings were analyzed on a LSR-Fortessa™ (BD Biosciences) with conserved settings throughout the entire study and data were analyzed using FlowJo™ Software (Tree Star v10.4).

Group "PsA patients"

Patients with Psoriatic Arthritis (PsA) fulfilling the Classification for PsA (CASPAR) criteria.

Multi-parametric Flow Cytometry analysis on patients and healthy donors samples

Intervention Type: OTHER

Collection of venous blood (16 mL) and synovial fluid (when available) samples, for each patient, at inclusion and in the frame of the usual medical follow-up at 3 months and between 6 and 12 months, before the onset of MTX (untreated patients) or during the course of MTX treatment (MTX-treated patients).

Collection of anonymous healthy donors blood samples, age- and sex-matched, obtained from the Etablissement Français du Sang.

Multi-parametric Flow Cytometry analysis was performed on these samples to assess CD73 expression on total memory T cells and within T helper lymphocyte subsets, their cytokine production and AMPase functions. For FoxP3 intracellular staining, cells were treated using the FoxP3 Fixation and Permeabilization kit (Life Technologies), according to manufacturer instructions. Stainings were analyzed on a LSR-Fortessa™ (BD Biosciences) with conserved settings throughout the entire study and data were analyzed using FlowJo™ Software (Tree Star v10.4).

Group "Healthy donors"

Anonymous healthy donors from the Etablissement Français du Sang.

Multi-parametric Flow Cytometry analysis on patients and healthy donors samples

Intervention Type: OTHER

Collection of venous blood (16 mL) and synovial fluid (when available) samples, for each patient, at inclusion and in the frame of the usual medical follow-up at 3 months and between 6 and 12 months, before the onset of MTX (untreated patients) or during the course of MTX treatment (MTX-treated patients).

Collection of anonymous healthy donors blood samples, age- and sex-matched, obtained from the Etablissement Français du Sang.

Multi-parametric Flow Cytometry analysis was performed on these samples to assess CD73 expression on total memory T cells and within T helper lymphocyte subsets, their cytokine production and AMPase functions. For FoxP3 intracellular staining, cells were treated using the FoxP3 Fixation and Permeabilization kit (Life Technologies), according to manufacturer instructions. Stainings were analyzed on a LSR-Fortessa™ (BD Biosciences) with conserved settings throughout the entire study and data were analyzed using FlowJo™ Software (Tree Star v10.4).

Interventions

Multi-parametric Flow Cytometry analysis on patients and healthy donors samples

Collection of venous blood (16 mL) and synovial fluid (when available) samples, for each patient, at inclusion and in the frame of the usual medical follow-up at 3 months and between 6 and 12 months, before the onset of MTX (untreated patients) or during the course of MTX treatment (MTX-treated patients).

Collection of anonymous healthy donors blood samples, age- and sex-matched, obtained from the Etablissement Français du Sang.

Multi-parametric Flow Cytometry analysis was performed on these samples to assess CD73 expression on total memory T cells and within T helper lymphocyte subsets, their cytokine production and AMPase functions. For FoxP3 intracellular staining, cells were treated using the FoxP3 Fixation and Permeabilization kit (Life Technologies), according to manufacturer instructions. Stainings were analyzed on a LSR-Fortessa™ (BD Biosciences) with conserved settings throughout the entire study and data were analyzed using FlowJo™ Software (Tree Star v10.4).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients aged ≥ 18 years
• Patients naive to biologics
• Patients with RA fulfilling the American College of Rheumatology and European League Against Rheumatism 2009 criteria
• Patients with PsA fulfilling the Classification for PsA (CASPAR) criteria

Exclusion Criteria

• None

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Service de Rhumatologie, Centre Hospitalier Lyon-Sud (HCL)

Pierre-Bénite, , France

Countries

France

Other Identifiers

LAdoRIC

Identifier Type: -

Identifier Source: org_study_id