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IgG from patients with pulmonary arterial hypertension and/or systemic sclerosis binds to vascular smooth muscle cells and induces cell contraction
  1. Guillaume Bussone1,2,3,
  2. Mathieu C Tamby1,2,3,
  3. Cynthia Calzas1,2,3,
  4. Nada Kherbeck1,2,3,
  5. Younes Sahbatou1,2,3,
  6. Claire Sanson1,2,3,
  7. Khaldoun Ghazal1,2,3,
  8. Hanadi Dib1,2,3,
  9. Babette B Weksler4,
  10. Cédric Broussard1,2,3,5,
  11. Franck Verrecchia6,
  12. Azzedine Yaici7,8,
  13. Véronique Witko-Sarsat1,2,3,
  14. Gérald Simonneau7,8,
  15. Loïc Guillevin9,
  16. Marc Humbert7,8,
  17. Luc Mouthon1,2,3,9
  1. 1INSERM U1016, Institut Cochin, Paris, France
  2. 2CNRS UMR 8104, Paris, France
  3. 3Université Paris Descartes, Paris, France
  4. 4Division of Hematology-Medical Oncology, Weill Medical College of Cornell University, New York, New York, USA
  5. 5Plate-forme Protéomique, INSERM U1016, Institut Cochin, Paris, France
  6. 6Université Nantes Atlantique and INSERM U957, Nantes, France
  7. 7Université Paris Sud, Faculté de Médecine, Centre National de Référence de l'Hypertension Artérielle Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, Assistance Publique-Hôpitaux de Paris, Clamart, France
  8. 8INSERM U999, Hypertension Artérielle Pulmonaire, Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France
  9. 9Université Paris Descartes, Faculté de Médecine, pôle de Médecine Interne and Centre de Référence pour les Vascularites Nécrosantes et la Sclérodermie Systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
  1. Correspondence to Dr Luc Mouthon, Institut Cochin, Pavillon Gustave Roussy, 4ème étage, 8 rue Méchain, 75014 Paris, France; luc.mouthon{at}


Objectives Pulmonary arterial hypertension (PAH) is characterised by remodelling of pulmonary arteries with enhanced vascular smooth muscle cell (VSMC) contraction, migration and proliferation. The authors investigated the presence of antibodies to human VSMCs in the serum of patients with systemic sclerosis with or without PAH and idiopathic PAH (iPAH).

Methods and results Antibodies to VSMCs were detected by immunofluorescence in sera from healthy controls and patients with scleroderma without PAH, scleroderma-associated PAH and iPAH. Serum IgG from these patients induced contraction of VSMCs in a collagen matrix in contrast with IgG from healthy controls. Several protein spots of interest and target antigens were identified by two-dimensional immunoblotting and MS, including stress-induced phosphoprotein 1 and α-enolase. Finally, antibodies to stress-induced phosphoprotein 1 were detected by ELISA in sera from 84%, 76% and 24% of patients with scleroderma without PAH, scleroderma-associated PAH and iPAH, respectively, compared with only 3% of healthy controls.

Conclusion The authors have identified IgG that binds to VSMCs in the serum of patients with scleroderma and iPAH. These antibodies may be pathogenic by modulating vascular contraction. The target antigens of these antibodies are stress-induced phosphoprotein 1 and α-enolase.

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  • GB, MCT and CC contributed equally to this work

  • Funding This work was supported by grants to the following individuals. GB received financial support from Avenir Mutualiste des Professions Libérales & Indépendantes (AMPLI), the Société Nationale Française de Médecine Interne, the Fonds d'Etudes et de Recherche du Corps Médical des hôpitaux de Paris and the Direction Régionale des Affaires Sanitaires et Sociales d'Ile-de-France. MCT received a grant from Pfizer and from the Direction de la Recherche Clinique of the Assistance Publique-Hôpitaux de Paris (PHRC National Auto-HTAP). CC received financial support from Association pour la Recherche en Médecine Interne et Immunologie Clinique (ARMIIC). YS received a grant from Pfizer and from the Direction de la Recherche Clinique of the Assistance Publique-Hôpitaux de Paris (CIRC 05066 HTAP-Ig). HD received financial support from AMPLI and ARMIIC.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics committee of Cochin Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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