Benjamin Thoreau, Arthur Ranaud, Philippe Chafey, Guilhem Clary, Morgane La Gall, Cédric Broussard, Odile Launay, David Launay, Eric Hachulla, Christophe Deligny, Alban-Elouen Baruteau, Anaïs Vallet-Pichard, Benjamin Chaigne, Azzeddine Yaici, Oliver Sitbon, David Montani, Marc Humbert, Luc Mouthon
Université Paris Cité. Hôpital Cochin and Assistance Publique-Hôpitaux de Pari. de l’Est et de l’Ouest. Hôpital Pierre Zobda-Quitman. Nantes Université. Université Paris-Saclay and Hôpital de Bicêtre.
France
Rheumatology
Rheumatology 2025;
DOI: 10.1093/rheumatology/keaf075
Abstract
Objectives: Pulmonary arterial hypertension (PAH) is a rare disease that may be associated with connective tissue diseases (CTD). Anti-fibroblast (AFA) and anti-endothelial cell autoantibodies (AECA) have been identified in idiopathic and systemic sclerosis (SSc)-associated PAH. The aim was to identify autoantibodies discriminating for PAH associated with systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) and primary Sjögren’s syndrome (SS), and their target antigens.
Methods: Sera were collected in the French multicentre Auto-HTAP study from 86 patients with CTD excluding SSc, including 32 with PAH (PAH+) and 54 without (PAH-). AFA and AECA were identified using one (1D) and two dimensions (2D) immunoblots and proteomics. ELISA tests using human recombinant proteins were used to confirm PAH-associated IgG reactivities.
Results: PAH+ patients had similar IgG AFA and AECA reactivities in 56.2% and 40.6% of the cases in 1D immunoblots, respectively. In 2D immunoblots, serum IgG pools from SLE patients (n = 14), MCTD (n = 10), SS (n = 9) and 14 healthy controls (n = 1) recognized respectively 273 ± 79, 205 ± 77, 109 ± 11 and 109 protein spots in fibroblasts and 189 ± 48, 146 ± 30, 88 ± 33 and 190 protein spots in endothelial cell extracts. Serum IgG from PAH+ patients recognized 39 fibroblast and 34 endothelial cell protein spots that were not recognized by IgG from PAH- patients, including Annexin A5 (ANXA5). Anti-ANXA5 IgG reactivity was significantly higher in PAH+ compared with PAH- patients with MCTD (73% vs 0%, p< 0.001) and SLE (33% vs 0%, p= 0.009).
Conclusion: Anti-ANXA5 IgG autoantibody reactivity might represent a predictive biomarker for PAH associated with MCTD and SLE.
Category
Class I. Pulmonary Hypertension Associated with Connective Tissue Disease
Potential Biomarkers Associated with Pulmonary Vascular Disease
Acquired Patient Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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