Ignite Creation Date:
2024-05-05 @ 10:53 PM
Last Modification Date:
2024-10-26 @ 10:25 AM
Study NCT ID:
NCT01208792
Status:
COMPLETED
Last Update Posted:
2017-08-14
First Post:
2010-07-12
Brief Title:
Auto-immunity and Pulmonary Arterial Hypertension
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Auto-immunity and Prognosis of Pulmonary Arterial Hypertension
Status:
COMPLETED
Status Verified Date:
2017-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Auto-HTAP
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 Sjögrens syndrome
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 Sjögrens syndrome
Detailed Description:
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 Sjögrens 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 Sjögrens 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 then distinguish subpopulations of PAH patients whose serum or purified IgG possibly specific for a given antigen are able to induce ROS production or cell proliferation For the population of ROS-producer patients we will correlate the clinical response to vasodilatator therapy to results of in VITRO inhibition experiments with vasodilatators and anti-oxidant molecules
Perspectives The characterization of target antigens of EC fibroblasts and vascular SMC specifically
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 Sjögrens 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 then distinguish subpopulations of PAH patients whose serum or purified IgG possibly specific for a given antigen are able to induce ROS production or cell proliferation For the population of ROS-producer patients we will correlate the clinical response to vasodilatator therapy to results of in VITRO inhibition experiments with vasodilatators and anti-oxidant molecules
Perspectives The characterization of target antigens of EC fibroblasts and vascular SMC specifically
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None