Antiphospholipid Antibodies: A Heterogenous Family of Autoantibodies
abstracts & commentary
Sources: Toschi V, et al. High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause. Stroke 1998;29:1759-1764; Tanne D, et al. Antiphospholipid-protein antibodies and ischemic stroke: Not just cardiolipin anymore (Editorial). Stroke 1998;29:1755-1758.
Antiphospholipid antibodies (apl) have been associated with a variety of clinical syndromes including ischemic stroke, deep vein thrombosis, recurrent miscarriages, thrombocytopenia, livido reticularis, left-sided cardiac valve lesions, and systemic lupus erythematosus (SLE). Anticardiolipin antibodies (aCL) and the lupus anticoagulant (LA) are the best known aPL, but there are others that also may promote coagulation.
Toschi and associates assessed the prevalence of aPL to noncardiolipin epitopes in 77 non-SLE patients with cerebrovascular disease of undetermined etiology who were younger than 51 years old. APL were characterized by enzyme-linked immunoabsorbent assay (ELISA) using seven different phospholipids.
Thirty-four patients (44%) had antibodies to one or more antigens: 29% to phosphatidylinositol (PI), 23% to cardiolipin, 18% to phosphatidylserine, 16% to phosphatidylglycerol, and 14% to phosphatidic acid. Forty-three patients (56%) tested negative for all phospholipid antigens.
Fifty-nine patients (77%) were aCL negative, and, of these, 23% had aPL to noncardiolipin phospholipids. APL to PI had the highest prevalence and in six of 22 patients with aPL-PI, anti-PI antibodies were the only ones detected. The LA was tested for in 66 of 77 patients and was found in only three. There were no significant differences in age, sex, diagnosis (stroke or TIA), or cerebrovascular risk factors between patients who had aPL to a single phospholipid and those who had aPL to multiple phospholipid antigens.
Toschi et al suggest that by assessing only aCL and LA in young stroke patients, physicians may be underestimating the prevalence of aPL to noncardiolipin phospholipids.
In an editorial, Tanne et al point out that aPL are a heterogeneous family of autoantibodies. The LA is more specific than the aCL for patients at risk for embolic stroke. Anticardiolipin antibodies are nonspecific and can be found in healthy individuals as well as those with infectious diseases or malignancies. In stroke patients, the IgG epitope of aCL has been implicated in thrombosis. The presence of certain aPL to noncardiolipin phospholipids may also alter the threshold for thrombosis and, thus, predispose to myocardial infarction and stroke. The specificity of the different aPL to thrombosis in the venous or arterial circulation is under investigation.
Commentary
The present report indicates an association between aPL to noncardiolipin antigens and cerebrovascular events in non-SLE patients. Currently used ELISA methods based on cardiolipin as the target antigen are not sensitive enough to detect all aPL-positive patients. Therefore, in patients with negative tests for aCL and LA, despite a clinical presentation that strongly suggests the presence of the aPL syndrome, further testing for antibodies to noncardiolipin phospholipids may be indicated. Nevertheless, for the present, the clinical use of the new immunoassays for antibodies against other phospholipids must be established before they can be recommended as part of the screening battery in cryptogenic stroke cases.
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