title: IgG from patients with pulmonary arterial hypertension and/or systemic sclerosis binds to vascular smooth muscle cells and induces cell contraction.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM U, Institut Cochin, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bussone
authors.forename: Mathieu C
authors.initials: MC
authors.lastname: Tamby
authors.forename: Cynthia
authors.initials: C
authors.lastname: Calzas
authors.forename: Nada
authors.initials: N
authors.lastname: Kherbeck
authors.forename: Younes
authors.initials: Y
authors.lastname: Sahbatou
authors.forename: Claire
authors.initials: C
authors.lastname: Sanson
authors.forename: Khaldoun
authors.initials: K
authors.lastname: Ghazal
authors.forename: Hanadi
authors.initials: H
authors.lastname: Dib
authors.forename: Babette B
authors.initials: BB
authors.lastname: Weksler
authors.forename: Cédric
authors.initials: C
authors.lastname: Broussard
authors.forename: Franck
authors.initials: F
authors.lastname: Verrecchia
authors.forename: Azzedine
authors.initials: A
authors.lastname: Yaici
authors.forename: Véronique
authors.initials: V
authors.lastname: Witko-Sarsat
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; D000368:Aged; D001324:Autoantigens / Q000032:analysis / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000150:complications / Q000276:immunology*; D055815:Young Adult
chemical_list: D001324:Autoantigens; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; C079373:STIP1 protein, human; D003094:Collagen