title: Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Laboratoire d'Immunologie, UPRES EA 4058, Pavillon Gustave Roussy, 4e étage, Paris-Descartes University, 8 rue Méchain, 75014 Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Terrier
authors.forename: Mathieu C
authors.initials: MC
authors.lastname: Tamby
authors.forename: Luc
authors.initials: L
authors.lastname: Camoin
authors.forename: Philippe
authors.initials: P
authors.lastname: Guilpain
authors.forename: Cédric
authors.initials: C
authors.lastname: Broussard
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bussone
authors.forename: Azzedine
authors.initials: A
authors.lastname: Yaïci
authors.forename: Françoise
authors.initials: F
authors.lastname: Hotellier
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000276:immunology*; D007074:Immunoglobulin G; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D011651:Pulmonary Artery / Q000166:cytology / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000150:complications / Q000276:immunology*
chemical_list: D000941:Antigens; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G