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  • Antifibroblast antibodies from systemic sclerosis patients bind to α-enolase and are associated with interstitial lung disease

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Basic and translational research
Extended report
Antifibroblast antibodies from systemic sclerosis patients bind to α-enolase and are associated with interstitial lung disease
  1. B Terrier1,
  2. M C Tamby1,
  3. L Camoin3,4,
  4. P Guilpain1,2,
  5. A Bérezné2,
  6. N Tamas1,
  7. C Broussard3,4,
  8. F Hotellier3,4,
  9. M Humbert5,
  10. G Simonneau5,
  11. L Guillevin2,
  12. L Mouthon1,2
  1. 1
    Paris Descartes University, Faculty of Medicine, UPRES EA 4058, Paris, France
  2. 2
    Paris Descartes University, Faculty of Medicine, Department of Internal Medicine and Reference Center for Necrotizing Vasculitis and Systemic Sclerosis, Cochin Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
  3. 3
    Cochin Institute, Paris Descartes University, CNRS (UMR 8104), Plate-Forme Protéomique Paris 5, Paris, France
  4. 4
    Inserm U567, Paris, France
  5. 5
    Paris Sud University, Faculty of Medicine, Department of Pneumology and French Reference Center for Pulmonary Arterial Hypertension, Antoine-Béclère Hospital, AP-HP, Clamart, France
  1. Correspondence to Dr L Mouthon, Laboratoire d’Immunologie, UPRES EA 4058, Pavillon Gustave Roussy, 4e étage, Université Paris Descartes, 8 rue Méchain, 75014 Paris, France; luc.mouthon{at}cch.aphp.fr

Abstract

Objective: To identify target antigens of antifibroblast antibodies (AFA) in systemic sclerosis (SSc) patients.

Patients and 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 α-enolase from Saccharomyces cerevisiae and recombinant human (rHu) α-enolase, respectively, on ELISA.

Results: In the first part, α-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 α-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HC had anti-rHu α-enolase antibodies (p = 0.001). In SSc, the presence of anti-S cerevisiae α-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 α-enolase testing.

Conclusion: In SSc, AFA recognise α-enolase and are associated with ILD and antitopoisomerase antibodies.

https://doi.org/10.1136/ard.2008.104299

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    Footnotes

    • ▸ Additional supplemental data are published online only at http://ard.bmj.com/content/vol69/issue2

    • Funding This work was supported by grants from the Association des Sclérodermiques de France (ASF), the Legs Poix, Chancellerie des Universités, Académie de Paris, France, Actelion Pharmaceuticals France and a “Contrat d’Investigation et de Recherche Clinique” (CIRC 05066) from the Assistance Publique-Hôpitaux de Paris. BT received financial support from the Direction Régionale de l’Action Sanitaire et Sociale (DRASS) d’Ile de France. MCT is a recipient of grants from Avenir Mutualiste des Professions Libérales and Indépendantes, ASF and Actelion Pharmaceuticals.

    • Competing interests None.

    • Ethics approval Ethics approval was obtained from the ethics committee of the La Pitié-Salpêtrière Hospital Group.

    • Patient consent Obtained.

    • Provenance and Peer review Not commissioned; externally peer reviewed.