title: Antifibroblast antibodies from systemic sclerosis patients bind to {alpha}-enolase and are associated with interstitial lung disease.
abstract: OBJECTIVE
  To identify target antigens of antifibroblast antibodies (AFA) in systemic sclerosis (SSc) patients.
  
  
  METHODS
  In the first part, sera from 24 SSc patients (12 with pulmonary arterial hypertension (PAH) and 12 without) and 36 idiopathic PAH patients, tested in pooled sera for groups of three, were compared with a sera pool from 14 healthy controls (HC). Serum IgG reactivity was analysed by the use of a two-dimensional electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for two groups: 158 SSc, 67 idiopathic PAH and 100 HC; and 35 SSc and 50 HC was tested against alpha-enolase from Saccharomyces cerevisiae and recombinant human (rHu) alpha-enolase, respectively, on ELISA.
  
  
  RESULTS
  In the first part, alpha-enolase was identified as a main target antigen of AFA from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) idiopathic PAH patients and 4/100 (4%) HC (p<0.001) had anti-S cerevisiae alpha-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HC had anti-rHu alpha-enolase antibodies (p = 0.001). In SSc, the presence of anti-S cerevisiae alpha-enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2% vs 89.7%; p<0.001) and diffusion capacity for carbon monoxide (47.4% vs 62.3%; p<0.001), and antitopoisomerase 1 antibodies (46% vs 21%; p = 0.005) but not anticentromere antibodies (11% vs 34%; p = 0.006). Results were similar with rHu alpha-enolase testing.
  
  
  CONCLUSIONS
  In SSc, AFA recognise alpha-enolase and are associated with ILD and antitopoisomerase antibodies.
authors.affiliation: Paris Descartes University, UPRES EA, France.
authors.forename: B
authors.initials: B
authors.lastname: Terrier
authors.forename: M C
authors.initials: MC
authors.lastname: Tamby
authors.forename: L
authors.initials: L
authors.lastname: Camoin
authors.forename: P
authors.initials: P
authors.lastname: Guilpain
authors.forename: A
authors.initials: A
authors.lastname: Bérezné
authors.forename: N
authors.initials: N
authors.lastname: Tamas
authors.forename: C
authors.initials: C
authors.lastname: Broussard
authors.forename: F
authors.initials: F
authors.lastname: Hotellier
authors.forename: M
authors.initials: M
authors.lastname: Humbert
authors.forename: G
authors.initials: G
authors.lastname: Simonneau
authors.forename: L
authors.initials: L
authors.lastname: Guillevin
authors.forename: L
authors.initials: L
authors.lastname: Mouthon
mesh_terms: D000328:Adult; D000368:Aged; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000097:blood; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000276:immunology*; D040901:Proteomics / Q000379:methods; D012595:Scleroderma, Systemic / Q000150:complications / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D010751:Phosphopyruvate Hydratase