Association of anticardiolipin antibodies with vascular injury: possible mechanisms
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- Dr Y S Haviv, Department of Nephrology, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem, Israel 91120 (email:havivyo{at}md2.huji.ac.il)
- Received 8 November 1999
- Accepted 16 February 2000
Lupus anticoagulant, first observed in 1952 in two patients with systemic lupus erythematosus (SLE),1 was linked to a phospholipid antigen when positive Wassermann tests for syphilis coincided with the lupus anticoagulant, documenting the lipid nature of the antigen. Bowie and colleagues were the first to unravel the paradoxical prothrombotic tendency of patients with positive lupus anticoagulant.2 This prothrombotic tendency that often results in microscopic thromboembolism is unique in being detected by positive serological tests. While immunoglobulins of isotypes IgG or IgM may have the lupus anticoagulant effect, the significance of IgA isotypes is not clear. These antibodies interfere with the in vitro phospholipid dependent coagulation tests. Lupus anticoagulant activity is documented by inability to correct prolonged activated partial thromboplastin time (aPTT) with normal plasma, and the necessity of phospholipid for the inhibition. Lupus anticoagulant belongs to a family of antiphospholipid antibodies (aPL) that also includes reagin and anticardiolipin antibodies (aCL), and the recently recognised antibody to beta-2-glycoprotein I (β2GpI). aCL and lupus anticoagulant are distinct and complementary tests for aPL. In patients with aPL syndrome, 60% will be positive for both lupus anticoagulant and aCL, while either test will be positive in the rest of the patients.
Until recently, the most sensitive test for aPL was aCL. This ELISA test determines antibody binding to solid plates coated with cardiolipin or other negatively charged phospholipids. Recently, aPL were shown to be specific for phospholipid-protein complexes,3 where the protein is identical with being β2GpI,4 5 or less often prothrombin, protein C, or protein S.6-8
aPL may be either autoimmune or alloimmune. The latter appear transiently after an infection or associated with a lymphoproliferative disorder, and do not usually have clinical implications.
The former are persistent and may be primary, as in the aPL syndrome, or secondary to …
