Clinical Trial: Auto-immunity and Pulmonary Arterial Hypertension

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Auto-immunity and Prognosis of Pulmonary Arterial Hypertension

Brief Summary:

The investigators have recently evidenced the presence of antibodies to endothelial cells and fibroblasts in patients with idiopathic or SSc-associated PAH. The investigators also have identified several target antigens of anti-fibroblasts antibodies.

The objective of this study is to further investigate for the presence of antibodies to endothelial cells and fibroblasts in patients and characterize the antigen specificity of autoantibodies in patients with different types of non idiopathic and non SSc-associated PAH, such as PAH associated with HIV infection, porto-pulmonary hypertension, congenital heart diseases, systemic lupus erythematosus, mixed connective tissue disease and Sjögren's syndrome


Detailed Summary:

Two hundred and fifty patients with PAH will be included: 65 patients with idiopathic PAH (iPAH), 20 with PAH associated with HIV infection, 20 with porto-pulmonary hypertension, 20 with PAH secondary to congenital heart disorders, 40 with SSc, 20 with SLE, 20 with MCTD and 10 with a PAH associated with a Sjögren's syndrome.

Two hundred patients without PAH will also be included: 80 patients with SSc and 20 in each of the following groups: HIV infection, porto-pulmonary hypertension, SLE, congenital heart disorders, MCTD and with Sjögren's syndrome.

Twenty patients with proximal chronic thromboembolic pulmonary hypertension (CTPH) will also be included in a control arm of the study.

Two hundred and fifty healthy blood donors age and sex-matched with patients with PAH, will be included as controls.

By using 2D-immunoblotting techniques, we will evidence IgG antibodies to fibroblasts, EC, vascular smooth muscle cells (SMC) in multiple groups of patients and we will characterize target antigens of these autoantibodies. We will also assess the production of ROS: nitric oxide (NO), hydrogen peroxide (H2O2) and the effect of the whole serum (and the IgG particularly) on in VITRO proliferation of EC, fibroblasts and vascular SMC. For sera that will induce the production of ROS, we will study the effect of different vasodilatator (prostacycline, endothelin receptor antagonist, type 5 phosphodiesterase inhibitors) and anti-oxidant therapies.

Expected results We will characterize target antigens of autoantibodies of patients with non-idiopathic and non SSc-associated PAH. We will compare these target to those previously identified in idiopathic or SSc-associated PAH. We will
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Immunological markers of prognosis interest in pulmonary arterial hypertension (PAH) [ Time Frame: one year ]

Original Primary Outcome: to identify immunological markers of prognosis interest in pulmonary arterial hypertension (PAH) [ Time Frame: one year ]

Current Secondary Outcome:

  • Target antigens of autoantibodies [ Time Frame: one year ]
    To characterize target antigens of autoantibodies in non-idiopathic and non-SSc associated PAH and to compare these target antigens to those recognized by autoantibodies directed at endothelial cells, fibroblasts and vascular smooth muscle cells in patients with idiopathic and SSc-associated PAH;
  • Subpopulations of patients with PAH whose serum is able to induce the production of reactive oxygen species (ROS) [ Time Frame: one year ]
    • To study and characterize subpopulations of patients with PAH whose serum is able to induce the production of reactive oxygen species (ROS) and/or cell proliferation.
    • In patients in whom the whole serum induces cell proliferation and ROS production in cell cultures, to correlate the results of inhibition experiments in vivo in the presence of vasodilators used in the treatment of PAH and clinical response to these vasodilators


Original Secondary Outcome:

  • To characterize target antigens of autoantibodies [ Time Frame: one year ]
    To characterize target antigens of autoantibodies in non-idiopathic and non-SSc associated PAH and to compare these target antigens to those recognized by autoantibodies directed at endothelial cells, fibroblasts and vascular smooth muscle cells in patients with idiopathic and SSc-associated PAH;
  • To study and characterize subpopulations of patients with PAH whose serum is able to induce the production of reactive oxygen species (ROS) [ Time Frame: one year ]
    • To study and characterize subpopulations of patients with PAH whose serum is able to induce the production of reactive oxygen species (ROS) and/or cell proliferation.
    • In patients in whom the whole serum induces cell proliferation and ROS production in cell cultures, to correlate the results of inhibition experiments in vivo in the presence of vasodilators used in the treatment of PAH and clinical response to these vasodilators


Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: July 12, 2010
Date Started: June 2010
Date Completion: September 2016
Last Updated: July 5, 2016
Last Verified: July 2016