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.