Antiphospholipid Antibody Testing Update

Antibodies directed toward phosphatidylethanolamine (anti-PE) appear to occur particularly frequently in women with unexplained early fetal loss (UFL). Two studies have shown that the presence of anti-PE antibodies is a higher independent risk factor for early UFL than either aCL or anti-β2GPI antibodies.^22,23 Moreover, anti-PE antibodies have been reported as the only aPL antibodies found in cases of UFL (73%). Regarding thrombosis, which is the other main clinical feature of APS, a multicenter study conducted within the framework of the European Forum on aPL antibodies found the prevalence of anti-PE was 15% in patients with unexplained venous thrombosis; this specificity was found mainly as the sole aPL antibody.²⁴ At present, there is no accepted standardized method for the measurement of anti-PE, and the heterogeneity of these antibodies increases the difficulties in attaining such a goal. This problem significantly limits the utility of this assay. Hence, following current evidence, the evaluation of anti-PE antibodies can be suggested in patients with “seronegative” APS despite the absence of an accepted method for antibody detection. Further studies are necessary to establish the place of these antibodies in the diagnostic algorithm for APS, including standardization and proper validation of an anti-PE ELISA test and a prospective clinical study on a broad population with APS.

Anti-β2GPI antibodies are a heterogeneous population of antibodies with reactivity toward different epitopes on β2GPI.²⁵ Among specificities to these epitopes, antibodies to domain I (DI) and anti-DI antibodies are more frequently associated with thrombosis and pregnancy morbidity compared with other anti-β2GPI antibodies; this finding has been confirmed in a recent double-blind multicenter study including 422 patients all positive for anti-β2GPI antibodies.²⁶ However, since the role of anti-DI antibodies in pathogenesis has been demonstrated only in animal models, further studies are needed before the anti-DI assay can be added to the diagnostic guidelines.²⁷

The current criteria aPL antibodies do not consider IgA isotypes for the aCL and anti-β2GPI tests. Several groups have investigated the prevalence of IgA aCL antibodies in SLE and APS patients and the relationship of these antibodies to clinical manifestations of APS. In unselected patients with SLE, the prevalence of increased titers of IgA aCL has been reported to vary from 1% to 44%.^28,29 Interestingly, the ethnic background of patients may influence the distribution of aCL isotypes. Molina and colleagues compared the prevalence of IgA aCL in African-American, Afro-Caribbean, and Hispanic patients with SLE and found a higher rate in the Afro-Caribbean population (21% compared with 16% of the American-Americans and 14% of the Hispanic population). Furthermore, aCL IgA was the only isotype present in 82% of aCL-positive Afro-Caribbean patients.³⁰