Detection of multiple annexin autoantibodies in a patient with recurrent miscarriages, fulminant stroke and seronegative antiphospholipid syndrome.

Philipp Scholz,Markus Auler,Peter Mallman,Thomas Streichert,Bent Brachvogel,Thomas Benzing,Andreas R Klatt

doi:10.11613/bm.2016.032

Abstract

Anti-phospholipid syndrome (APS) is one of the main causes for recurrent miscarriages. The diagnosis of APS is based on the occurrence of clinical symptoms such as thrombotic events or obstetric complications as well as the detection of antiphospholipid antibodies directed against β2-glycoprotein I and cardiolipin, or a positive lupus anticoagulant assay. However, there is a subpopulation of patients with clinical symptoms of APS, but the lack of serological markers (seronegative APS). In addition, a large proportion of patients with unexplained recurrent miscarriages exist. These cases may be attributed, at least in part, to a seronegative APS. The presence of autoantibodies against annexins is potentially associated with APS. Here we used immunoassays and immunoblots to detect autoantibodies directed against annexin A1-5, and A8, respectively, in a patient with a seronegative APS and a history of six recurrent pregnancy losses and fulminant stroke. We found strong IgM isotype antibody reactivity directed against annexin A2 and annexin A8, and moderate to weak IgM isotype antibody reactivity directed against annexin A1, A3, and A5. Further studies will evaluate the diagnostic value of IgM isotype antibodies against annexin A1-A5, and A8 for seronegative APS and recurrent miscarriages.

Highlights

Anti-phospholipid syndrome (APS) is an autoimmune disorder that leads to a hypercoagulative state
There is an emerging group of autoantibodies potentially associated with APS [10]. These autoantibodies are directed against proteins involved in coagulation, or cell membrane binding, but their clinical utility and diagnostic value remain unclear. This leads to a diagnostic gap in patients with clinical symptoms of an APS, but without evidence of established serological markers, and may have fatal consequences for the patients
We report the case of a woman diagnosed with seronegative APS and a history of six pregnancy losses and fulminant stroke, with no evidence of the diagnostic relevant aPL antibodies, but with persisting high IgM isotype autoantibodies reactivity against AnxA2 and AnxA8

Summary

Introduction

Anti-phospholipid syndrome (APS) is an autoimmune disorder that leads to a hypercoagulative state. This disorder is characterized by any thrombotic event and/or specific obstetric complications, for instance preterm delivery and recurrent miscarriages [1,2,3]. APS is one of the main causes for pregnancy failure. The presence of persistent circulating antiphospholipid antibodies (aPL) is used for the diagnosis of APS. Antiphospholipid antibodies are a heterogeneous family of autoantibodies against proteins binding to negatively charged phospholipids.

Methods

Results

Conclusion