Abstract

The present study was conducted to diagnose obstetric anti-phospholipid syndrome (OAPS) in patients with clinical signs suggestive of anti-phospholipid syndrome (APS), but persistently negative for conventional anti-phospholipid antibodies (aPL). Sera from 61 obstetrical seronegative APS (SN-APS) patients were analyzed for anti-cardiolipin antibodies (aCL) using thin-layer chromatography (TLC)-immunostaining, for anti-cardiolipin/vimentin antibodies (aCL/Vim), anti-phosphatidylserine/prothrombin antibodies, IgA anti-β2glycoprotein I antibodies (aβ2GPI), and IgA aCL antibodies by enzyme-linked immunosorbent assay. Taken together, our findings show that in 50 out of 61 SN-APS (81.9%) at least one aPL/cofactor antibody was detected using the assays under test. Results revealed that 76% of SN-APS patients resulted positive for aCL by TLC-immunostaining, 54% for aCL/Vim, 12% for aPS/PT, 4% for IgA aβ2GPI, and 2% for IgA aCL. Thirty-five out of 61 patients were followed up and the tests were repeated on two occasions, at least 12 weeks apart. Twenty-six out of 35 SN-APS (74.3%) were positive at least one non-conventional test; only 2 patients (5.7%) did not confirm the positivity to the second test. These findings suggest that non-conventional tests, mainly aCL/Vim and aCL detected by TLC-immunostaining, seem to be the most sensitive approaches for finding out aPL in patients with obstetric SN-APS. The use of these tests can be useful for accurate and timely diagnosis of patients with obstetrical APS who are negative for conventional laboratory criteria markers.

Highlights

  • Anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis and pregnancy morbidity associated with circulating antiphospholipid antibodies [1]

  • Differences were not observed in the prevalence of obstetric events, including early spontaneous abortions, fetal deaths, prematurity, or pre-eclampsia, between women with seronegative APS” (SN-APS) and seropositive APS (SP-APS) [14]

  • Since APS is recognized as the most common treatable cause of recurrent miscarriage, for women with a history of recurrent early abortions or fetal loss, a diagnosis of APS addresses them toward treatments, which significantly improve the rate of live births [15]

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Summary

Introduction

Anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis and pregnancy morbidity associated with circulating antiphospholipid antibodies (aPL) [1]. Obstetrical APS (OAPS) is characterized by early recurrent miscarriage, unexplained fetal loss, and/or premature birth due to eclampsia, preeclampsia, or placental insufficiency as stated in the classification criteria for definite APS [2]. New antigenic targets or methodological approaches to detect aPL in SN-APS have been investigated and several non-conventional anti-phospholipid antibodies have been described [8, 9]. With a proteomic approach, we identified cardiolipin/vimentin (CL/Vim) as a “new” target for APS, detectable in SN-APS patients [10]. It has demonstrated the possibility of detecting aPL in SN-APS patients by immunostaining on thin-layer chromatography (TLC) plates [11, 12]

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