This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200707-1015OCv1 177/10/1128    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Terrier, B. Articles by Mouthon, L. PubMed PubMed Citation Articles by Terrier, B. Articles by Mouthon, L.

Identification of Target Antigens of Antifibroblast Antibodies in Pulmonary Arterial Hypertension

¹ Paris Descartes University, Faculty of Medicine, UPRES-EA 4058, Paris, France; ² Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Laboratory of Proteomics, Paris, France; ³ Faculty of Medicine, Paris Sud University, Department of Pneumology and French Reference Center for Pulmonary Arterial Hypertension, Antoine-Beclere Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Clamart, France; ⁴ Faculty of Medicine, Paris Descartes University, Department of Internal Medicine and French Reference Center for Necrotizing Vasculitides and Systemic Sclerosis, Cochin Hospital, AP-HP, Paris, France; and ⁵ INSERM, U567, Paris, France

Correspondence and requests for reprints should be addressed to Dr. Luc Mouthon, M.D., Ph.D., Laboratoire d'Immunologie, UPRES EA 4058, Pavillon Gustave Roussy, 4e étage, Paris-Descartes University, 8 rue Méchain, 75014 Paris, France. E-mail: luc.mouthon{at}cch.aphp.fr

Rationale: Pulmonary arterial hypertension (PAH) may be classified as idiopathic (IPAH) or familial (FPAH) or associated with various conditions and exposures such as dexfenfluramine intake (Dex-PAH) or systemic sclerosis (SSc-PAH). Because fibroblast dysfunction has been identified in SSc and IPAH and antifibroblast antibodies (AFAs) with a pathogenic role have been detected in the serum of SSc patients, we used a proteomic approach combining two-dimensional electrophoresis and immunoblotting to identify the target antigens of AFAs in such patients.

Objectives: To identify target antigens of antifibroblast antibodies in pulmonary arterial hypertension.

Methods: Sera from 24 patients with IPAH, 6 with FPAH, 6 with Dex-PAH, and 12 with SSc-PAH were collected. We pooled sera from sets of three patients with PAH classification and SSc-PAH based on autoantibody profile. Sera from 14 healthy blood donors were also pooled and used as a control.

Measurements and Main Results: Serum IgG antibodies in the pools of patients with IPAH (n = 8), FPAH (n = 2), Dex-PAH (n = 2), and SSc-PAH (n = 4) recognized 103 ± 31, 63 ± 20, 78 ± 11, and 81 ± 12 protein spots, respectively, whereas serum IgG antibodies from healthy control subjects recognized 43 ± 22 protein spots. Twenty-one protein spots were specifically recognized by the serum IgG antibodies from patients with PAH. We identified 16 of the protein spots as vimentin, calumenin, tropomyosin 1, heat shock proteins 27 and 70, glucose-6-phosphate-dehydrogenase, phosphatidylinositol 3-kinase, DAP kinase, and others. These proteins are involved in regulation of cytoskeletal function, cell contraction, oxidative stress, cell energy metabolism, and other key cellular pathways.

Conclusions: AFAs detected in patients with PAH recognize cellular targets playing key roles in cell biology and maintenance of homeostasis.

Key Words: fibroblast • antigens • autoantibodies • pulmonary arterial hypertension

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Antifibroblast antibodies have previously been described in patients with pulmonary arterial hypertension and systemic sclerosis. However, the target antigens of these antibodies are unknown. What This Study Adds to the Field We identified target antigens of antifibroblast antibodies detected in patients with pulmonary arterial hypertension. These antibodies recognize cellular targets playing key roles in cell biology and maintenance of homeostasis.