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Antiphospholipid Antibody Testing Update

Staff  |  Issue: January 2012  |  January 13, 2012

In another study, Cucurull and colleagues demonstrated the presence of IgA aCL in more than half of the patients with APS, although most of them were also positive for IgG and IgM; these findings suggest that testing for IgA would add little diagnostic information beyond that provided by IgG and IgM determinations.31 In the same study, the authors demonstrated an association between elevated levels of IgA aCL antibodies and clinical manifestations of APS. Interestingly, IgA aCL antibodies have been shown to be thrombogenic in mice.4 Thus, most of data indicate that isolated IgA aCL positivity is rare but may be associated with clinical manifestations of APS. Considering the low prevalence of IgA aCL positivity alone, IgA aCL testing should be performed only in cases where IgG and IgM aCL tests are negative but the suspicion of APS is high.

Several studies have investigated the association between IgA anti-β2GPI and clinical features of APS. Yamada and colleagues have found IgA anti-β2GPI positivity in a subgroup of women with recurrent pregnancy loss who were nevertheless negative for IgG anti-β2GPI.32 These antibodies likely bind to domain IV and domain V of β2GPI, which may contribute to thrombosis.33 Kumar and colleagues reported five cases of patients with clinical manifestations of APS but positivity only for IgA anti-β2GPI.34 Recently, a group of investigators from Dr. Pierangeli’s laboratory analyzed the prevalence of isolated IgA anti-β2GPI in three different cohorts: two SLE cohorts composed of 588 and 200 participants, respectively, and 5,098 individuals referred between January 2008 and March 2010 to the investigator’s laboratory for APS work-up (APLS). The authors found that 35, 15, and 25 participants from the three cohorts, respectively, were positive exclusively for IgA anti-β2GPI while negative for all the other aPL antibodies, including IgA aCL. Importantly, the majority of those patients (70% to 100%) had clinical features of APS. Furthermore, IgA anti-β2GPI antibodies have recently been found to be an independent risk factor for acute myocardial infarction and acute cerebral ischemia in populations without APS.35

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In view of these findings, the task force recommended that IgA anti-β2GPI should be tested in the presence of clinical features of APS or SLE, particularly when other tests are negative. In addition, well-designed studies, which should include evaluation and comparison of multiple available assays in large populations of patients, are needed to confirm the diagnostic value of this test.

To address the challenges on aPL antibidy testing, an international criteria APL task force of researchers and scientific leaders in the field was formed prior to the International Congress on Antiphospholipid Antibodies.

Recent studies have investigated the clinical relevance of antibodies binding to human prothrombin alone (aPT-A) or to prothrombin-phosphatidylserine complex (anti–PS-PT). Funke and colleagues reported that aPS-PT conferred an odds ratio of 2.8:1 for venous thrombosis and 4.1:1 for arterial thrombosis in patients with SLE.36 Atsumi and colleagues showed that aPS-PT conferred an odds ratio for APS of 3.6:1 in 265 Japanese patients with systemic autoimmune diseases.37 In recent years, at least two prospective studies have shown that the presence of aPT-A is a predictor of recurrent thrombosis in APS patients.38,39 A 15-year longitudinal study has identified IgG aPT-A as the most useful predictor of thrombosis in SLE patients.40 These tests have been shown to have higher specificity but decreased sensitivity for the diagnosis of APS compared with aCL. Nevertheless, the task force recognized that the main problem with aPT-A and/or anti–PS-PT ELISAs is the lack of standardization despite efforts and international initiatives. Although these tests may be useful in screening for the risk for thrombosis, the task force did not recommend their inclusion as one of the laboratory criteria of APS at this time.

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Filed under:ConditionsOther Rheumatic ConditionsResearch RheumSystemic Lupus Erythematosus Tagged with:Antiphospholipid Antibody Syndrome (APS)Hughes SyndromelabsLupusResearchrheumatologistSystemic lupus erythematosus

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