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Pulmonary hypertension
Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension
  1. M C Tamby1,2,
  2. Y Chanseaud1,2,
  3. M Humbert3,
  4. J Fermanian4,
  5. P Guilpain1,2,
  6. P Garcia-de-la-Peña-Lefebvre1,
  7. S Brunet1,
  8. A Servettaz2,
  9. B. Weill2,
  10. G Simonneau3,
  11. L Guillevin5,
  12. M C Boissier1,
  13. L Mouthon1,2,5
  1. 1UPRES-EA 3408, Laboratoire d’Immunopathologie et Immuno-intervention, UFR-SMBH Léonard de Vinci, Université Paris Nord, Bobigny, France
  2. 2UPRES-EA 1833, Laboratoire d’Immunologie, UFR Cochin-Port Royal, Université Paris V, Paris, France
  3. 3UPRES-EA 2705, Service de Pneumologie, Hôpital Antoine Béclère, Assistance Publique–Hôpitaux de Paris (AP-HP) et Université Paris Sud, Clamart, France
  4. 4Service de Biostatistiques, Hôpital Necker, AP-HP, Université Paris V, Paris, France
  5. 5Service de Médecine Interne, Hôpital Cochin, AP-HP et Université Paris V, Paris, France
  1. Correspondence to:
    Dr L Mouthon
    Laboratoire d’Immunologie, Pavillon Gustave Roussy, UFR Cochin-Port Royal, 8 rue Méchain, 75014 Paris, France; luc.mouthoncch.aphp.fr

Abstract

Background: It has previously been shown that IgG antibodies from patients with limited cutaneous systemic sclerosis (SSc) bind to specific microvascular endothelial cell antigens. Since patients with limited cutaneous SSc are prone to develop pulmonary arterial hypertension (PAH), and since endothelial cell activation is involved in the pathogenesis of idiopathic PAH (IPAH), a study was undertaken to examine the presence of anti-endothelial cell antibodies in patients with idiopathic or SSc associated PAH.

Methods: PAH was confirmed by right heart catheterisation (mean pulmonary artery pressure at rest >25 mm Hg). Serum IgG and IgM reactivities were analysed by immunoblotting on human macrovascular and microvascular lung and dermal endothelial cells from patients with IPAH (n = 35), patients with PAH associated with SSc (n = 10), patients with diffuse (n = 10) or limited cutaneous (n = 10) SSc without PAH, and 65 age and sex matched healthy individuals.

Results: IgG antibodies from patients with IPAH bound to a 36 kDa band in macrovascular endothelial cell extracts with a higher intensity than IgG from other patient groups and controls. IgG antibodies from patients with IPAH bound more strongly to a 58 kDa band in microvascular dermal endothelial cells and to a 53 kDa band in microvascular lung endothelial cells than IgG antibodies from other patients and controls. IgG antibodies from patients with limited cutaneous SSc with or without PAH, but not from other groups or from healthy controls, bound to two major bands (75 kDa and 85 kDa) in microvascular endothelial cells.

Conclusion: IgG antibodies from patients with idiopathic or SSc associated PAH express distinct reactivity profiles with macrovascular and microvascular endothelial cell antigens.

  • AECA, anti-endothelial cell antibodies
  • BMPR-II, bone morphogenetic protein receptor type II
  • HUVEC, human umbilical vein endothelial cells
  • HMVEC-d, human microvascular dermal endothelial cells
  • HMVEC-l, human microvascular lung endothelial cells
  • IPAH, idiopathic pulmonary arterial hypertension
  • PAH, pulmonary arterial hypertension
  • SSc, systemic sclerosis
  • pulmonary arterial hypertension
  • systemic sclerosis
  • anti-endothelial cell antibodies

https://doi.org/10.1136/thx.2004.029082

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    Footnotes

    • This work is supported by a grant from the Université Paris Nord (Bonus Qualité Recherche), INSERM (CReS #4CR08F), the Association des Sclérodermiques de France and the Legs POIX, Chancellerie des Universités, Académie de Paris, France. The study was supported in part by the French Network of Pulmonary Arterial Hypertension. M C Tamby is a recipient of a grant from AMPLI (Avenir Mutualiste des Professions Libérales & Indépendantes); Y Chanseaud was funded by the Ministère de l’Enseignement Supérieur et de la Recherche, France and the Laboratoire Français du Fractionnement et des Biotechnologies (LFB); P Garcia de la Peña-Lefebvre received a grant from the Association Claude-Bernard, France; A Servettaz received financial support from the Direction Régionale de l’Action Sanitaire et Sociale de la région Champagne-Ardennes, France.

    • Competing interests: none declared.

    • This work has been presented at the 3rd Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS), 15–19 May 2003, Paris, France; at the 4th Annual Congress of the European League Against Rheumatism (EULAR), 19–21 June 2003, Lisbon, Portugal; and at the 67th ACR/ARHP Annual Scientific Meeting, 24–28 October 2003, Orlando, Florida, USA.