Auto-immunity and Pulmonary Arterial Hypertension (Auto-HTAP)

Assistance Publique - Hôpitaux de Paris

Status

Completed

Conditions

Connective Tissue Disease

Systemic Sclerosis

HIV Infection

Congenital Heart Defect

Pulmonary Arterial Hypertension

Treatments

Procedure: skin biopsy

Other: Blood Sample

Study type

Interventional

Funder types

Other

Identifiers

NCT01208792

P071209

Details and patient eligibility

About

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

Full 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 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 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

Enrollment

629 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

age over 18

for PAH patients: pre-capillary PAH evidenced by right-heart catheterization
no associated systemic disease for idiopathic PAH patients
for HIV patients, HIV1 infection confirmed by ELISA and western blot
for patients with porto pulmonary hypertension: evidence by endoscopy of esophageal varices, confirmation of hepatic venous pressure gradient over 5 mmHg by catheterization of the hepatic veins
for patients with congenital heart defect: evidence by imaging of atrial or ventricular septal defect, or patent ductus arterious and confirmed by heart catheterization
patients with SSc will fulfill the American College of Rheumatology (ACR) and the LEROY and MEDSGER criteria
patients with MCTD will fulfill the criteria for MCTD
patients with SLE will fulfill the updated and revised ACR criteria
patients with Sjögren's syndrome will fulfill the American-European consensus group criteria
patients with chronic thromboembolic pulmonary hypertension: Lung scintiscan showing segmental mismatched perfusion defects and confirmation by angiography of the occlusion and the chance of success of endarterectomy according to the location of disease
Signed written informed consent
Patients with health insurance

Exclusion criteria

age under 18
pregnant women
absence of written informed consent
associated malignant tumor

Trial design

Primary purpose

Diagnostic

Allocation

Non-Randomized

Interventional model

Factorial Assignment

Masking

None (Open label)

629 participants in 3 patient groups

Disease group

Experimental group

Description:

Two hundred patients with PAH will be included: 50 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.

Treatment:

Other: Blood Sample

Procedure: skin biopsy

Control group 1

Other group

Description:

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

Treatment:

Other: Blood Sample

Control group 2

Other group

Description: