A noncriteria aPL task force assembled prior to the APLA 2010 Congress was charged by the congress chair to address, in an evidence-based manner, the status of various new tests under development for confirmation of the diagnosis of APS. The results and recommendations of that task force are discussed here and were also recently published elsewhere.14
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Explore This IssueJanuary 2012
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Noncriteria aPL Task Force Work and Recommendations
In addition to aCL, aPL antibodies are directed against negatively charged phospholipids. These antibodies include antiphosphatidic acid (anti-PA), antiphosphatidyinositol (anti-PI), antiphosphatidylserine (anti-PS), and antiphosphatidylglycerol. Furthermore, some antibodies can be detected by binding to a mixture of negatively charged phospholipids (APhL). Very few studies have been performed to determine the relevance of these antibody markers in clinical settings. Anti-PS and APhL have been the most extensively investigated in the settings of thrombosis and pregnancy morbidity, and both tests have been shown to be more specific for APS when compared with aCL.15-18
With regard to obstetrical manifestations of APS, various investigators have screened the sera of patients with recurrent pregnancy loss (RPL) to identify antibody specificities that might be missed if only aCL is tested. In a large retrospective study, Yetman and Kutteh determined the prevalence of aPL antibodies among 866 women with RPL compared with 288 controls. In this study, 150 of the women with RPL were positive for aCL (IgG and/or IgM), whereas 87 were negative for aCL, but positive for one of the other aPL antibodies.19 Hence, a significant number of the women with RPL would not have been identified if they had been tested only for aCL. In another study, the same group found anti-PS positivity in 49 of 872 women with RPL who were negative for aCL and LAC.20 Basic laboratory studies support the involvement of aPL other than aCL in obstetric APS: anti-PS antibodies have been shown to inhibit trophoblast development and invasion using an in vitro model system.21 These antibodies also may retard syncytiotrophoblast formation and decrease the synthesis of β-hCG.
Even for assays using the same reagents, however, the results of tests can be discordant, as there are no formal calibrators or accepted methods of detection. Hence, the current level of evidence does not warrant any changes to the current criteria and testing for anti-PA, anti-PI, and anti-PS antibodies in the initial diagnostic work-up for APS doesn’t appear clinically useful. Likely, anti-PS is the best candidate for further investigation, provided that an accepted and standardized method is in place.