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FRI0142 Correlation between high levels of antibodies directed against the domain 1 of calpastatin and the presence of vasculitis in systemic lupus erythematosus
  1. V Salle1,
  2. O Vittecoq1,
  3. F Jouen-Beades1,
  4. JF Ménard2,
  5. JP Ducroix3,
  6. M Godin4,
  7. X Le Loët1,
  8. F Tron1
  1. 1INSERM U-519
  2. 2Department of Biostatistics
  3. 3Department of Internal Medicine, CHU Amiens, Amiens, France
  4. 4Department of Nephrology, CHU Rouen, Rouen, France

Abstract

Background Calpastatin, an endogenous inhibitor of calpains, calcium-activated cysteine proteases, has been recently identified as a new auto-antigen.1,2 Anti-calpastatin antibodies (ACAST) have been detected in venous thrombosis,3 rheumatoid arthritis (RA) but also in other auto-immune diseases such as systemic lupus erythematosus (SLE), Sjogren syndrome or systemic sclerosis. The C-terminal 27 aminoacids fragment of calpastatin represents the major epitope recognised by these antibodies. However, other epitopes, particularly in the N-terminal region of the protein, including the domain 1 (D1), are targeted by antibodies in sera of RA patients.4 The clinical relevance of ACAST D1 in SLE remain unknown.

Objectives (i) to evaluate the prevalence of ACAST D1 in SLE; (ii) to correlate the presence of ACAST D1 with: 1- clinical manifestations and SLE activity index (SLEDAI); 2- anti-phospholipid antibodies (APL), i.e., anti-cardiolipin antibodies (ACL), lupus anticoagulant (LA), anti-beta2 glycoprotein I antibodies (aB2GPI), anti-annexin V antibodies (aANXV).

Methods 84 patients with SLE who fulfilled the revised ACR criteria were included retrospectively. The following clinical features were studied: arthritis, nephritis, neurological and cardiac manifestations, vascular injury (arterial and venous thrombosis, fetal losses, vasculitis). The diagnosis of vasculitis was made by histological and angiographic data. For detection of ACAST D1, an ELISA was performed, using as antigen the recombinant domain 1 of calpastatin. ACL, aB2GPI, aANXV have also been detected by ELISA.

Results The prevalence of ACAST D1, aB2GPI, aANXV, ACL and ACC was 9%, 14%, 12%, 43% and 48% respectively. Among the several clinical manifestations, the frequency of ACAST D1 was higher in vasculitis (23%). No statistically association was found between ACAST D1 and APL or the presence of thrombosis. However, high levels of ACAST D1 were positively correlated with the presence of vasculitis (p = 0.0085) and with disease activity (p < 0.02).

Conclusion ACAST D1 could participate in pathogenic mechanisms of inflammatory vascular lesions and could represent a marker of disease activity.

References

  1. Després, et al. J Clin Invest. 1995;95:1891–6

  2. Mimori, et al. Proc Natl Acad Sci USA. 1995;92:7267–71

  3. Schlosser, et al. Thromb Haemost. 1997;77:11–13

  4. Lackner KJ, et al. Br J Rheumatol. 1998;37:1164–71

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