Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Autoantibodies to Heat Shock Protein 60 Are Associated with Arterial Vascular Events in Patients with Anti-Phospholipid Antibodies
Dieude1, Mélanie, Correa1, José A., Neville1, Carolyn, Pineau1, Christian A., Levine2, Jerrold S., Subang1, Rebecca, Landolt-Marticorena3, C.
Anti-heat shock protein 60 autoantibodies (anti-HSP60) are associated with coronary artery disease and atherosclerosis, and are known to affect endothelial cells in vitro. However, their association with other vascular events (VE) remains unclear. We have recently shown that anti-HSP60 promote thrombosis in a murine model of arterial injury. Based on these findings, we hypothesized that the presence of anti-HSP60 autoantibodies, alone or in combination with other thrombogenic risk factors (e.g., anti-phospholipid antibodies [aPL]), would be associated with an elevated risk of VE.
The study population was derived from the databases of three ongoing cohort studies: two systemic lupus erythematosus (SLE) registries and one cohort of individuals with aPL. Only individuals with aPL testing performed on at least two occasions were included. aPL positivity was defined as: anti-cardiolipin (aCL) IgG/IgM >40 APL units, and/or lupus anticoagulant (LA) positive, and/or anti-b2-glycoprotein I (ab2GPI) IgG/IgM positive, each on >= 2 occasions >= 12 weeks apart. Data from a total of 406 participants was captured and four groups were identified: (1) aPL-positive with VE (n=85); (2) aPL-positive without VE (n=83); (3) aPL-negative with VE (n=119); and (4) aPL-negative without VE (n=119). Arterial VE (VE-A) (n=123) or venous VE (VE-V]) (n=97) were confirmed from medical records. Serum anti-HSP60 were determined by enzyme-linked immunoassay and values exceeding the 75th percentile of the healthy controls (n=25) were considered to be high-titer positive. Clinical and demographic variables captured included age, race, gender, family history of cardiovascular disease, smoking, SLE, hypertension, and diabetes mellitus.
Multivariate analyses revealed that total VE were associated solely with age or hypertension. However, analysis of the VE according to their origin showed an association of VE-A, but not VE-V, with anti-HSP60 (OR=2.326 [95% CI=1.1574.673]). Furthermore, the concomitant presence of aPL with anti-HSP60 increased the risk of VE-A (OR=6.19 [95% CI=2.0218.91]), but not VE-V (OR=1.09 [95% CI=0.363.28]). Finally, the presence of individual aPL (i.e., aCL, LA, or ab2GPI) with anti-HSP60 also increased the risk of VE-A, with the strongest association observed for aCL (OR=8.67 [95%CI=1.9738.08]).
Our results demonstrate that anti-HSP60 are associated with VE-A, and that the concomitant presence of aPL (particularly aCL) with anti-HSP60 further enhances the risk of these events.
To cite this abstract, please use the following information:
Dieude, Mélanie, Correa, José A., Neville, Carolyn, Pineau, Christian A., Levine, Jerrold S., Subang, Rebecca, et al; Autoantibodies to Heat Shock Protein 60 Are Associated with Arterial Vascular Events in Patients with Anti-Phospholipid Antibodies [abstract]. Arthritis Rheum 2009;60 Suppl 10 :2048