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

March 24, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Auto-immunity and Prognosis of Pulmonary Arterial Hypertension

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 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

Study Type

Interventional

Enrollment (Actual)

629

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clamart, France, 92000
        • Pneumology Department, Antoine Béclère Hospital
      • Lille, France, 59000
        • Internal Medicine Department, Claude Huriez Hospital
      • Paris, France, 75014
        • Internal Medicine Department, Cochin Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Disease group
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.
Other: Blood Sample
a blood sample will be collected
Procedure: skin biopsy
The biopsy site (usually the forearm) will be first cleaned, and then anesthetized with pain relieving (spray, cream, or injection). The skin is then sampled using a punch that takes a core (a small cylindrical fragment of tissue from the area of interest
Other: Control group 1
Two hundred healthy blood donors age and sex-matched with patients with PAH, will be included as controls.
Other: Blood Sample
a blood sample will be collected
Other: Control group 2
Twenty patients with proximal chronic thromboembolic pulmonary hypertension (CTPH) will also be included in a control arm of the study.
Other: Blood Sample
a blood sample will be collected

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Immunological markers of prognosis interest in pulmonary arterial hypertension (PAH)
Time Frame: one year
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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;
one year
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
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

Investigators

  • Principal Investigator: Luc Mouthon, MD, PhD, Assistance Publique Hopitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2010

Primary Completion (Actual)

July 15, 2014

Study Completion (Actual)

May 15, 2017

Study Registration Dates

First Submitted

July 12, 2010

First Submitted That Met QC Criteria

September 23, 2010

First Posted (Estimated)

September 24, 2010

Study Record Updates

Last Update Posted (Actual)

March 27, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P071209

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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