2001: A prospective, seasonal odyssey into antiphospholipid protein antibodies.

The human immune response is highly complex, dictated by incompletely understood genetic and environmental factors, and it appears to be important in contributing to several forms of cerebrovascular disease. Antiphospholipid-protein antibodies (aPL) have been implicated in immune-mediated clotting in both arterial and venous beds1 and are considered to be the most common hematological condition associated with ischemic stroke. However, given the vast number of conditions associated with aPL production, including systemic lupus erythematosus, HIV, syphilis, other infections, malignancy, immunizations, and medications, it is clear that aPL are quite a heterogeneous family of immunoglobulins that vary in specificity, isotype, subclass, titer, and associated mechanisms of action. aPL may also be seen in otherwise healthy individuals. Thus, there has been great difficulty is sorting out the potentially important aPL from the nonspecific immune system “noise.” A major breakthrough in the field came in 1990 when 3 groups identified the need for a cooperative phospholipid binding protein in order to detect most, but not all, aPL antibodies.2–4 Based on limited data, it has been suggested that infection-related aPL may be less pathogenic and that these aPL do not require a cofactor (apolipoprotein H, also called b2 glycoprotein-1 [b2GP1]) for their detection with ELISA. b2GP1 is a cationic plasma glycoprotein with a molecular mass of 50 kDa and a plasma concentration of '200 mg/mL. Cofactor-dependent aPL may allow identification of a more specific group of antibodies involved in thrombo-occlusive disease.1 These differences in aPL may also contribute to the lack of consistent data on their relationship to ischemic stroke (IS). Two new, intriguing, and important pieces to the aPL puzzle appear in this issue of Stroke. Both articles attempt to tease out the more specific from the nonspecific aPL using a nested case-control study design. A prospective study using cofactor-dependent anticardiolipin antibodies (aCL) has shown that these antibodies are independently associated with incident stroke and myocardial infarction (MI).5 The other article suggests that aPL may be expected to follow seasonal patterns hypothetically related to aPL produced in response to different stimuli.6 These 2 large, well-conducted epidemiological studies, in addition to the basic research supporting pathogenicity of aPL in thromSee articles on pages 1701 and 1707