Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in plasmas of patients with the antiphospholipid syndrome.
Annexin A5 (A5) forms 2-dimensional crystals over phospholipid bilayers, blocking their availability for coagulation reactions. Recently, human antiphospholipid (aPL) monoclonal antibodies (mAbs) have been demonstrated by atomic force microscopy (AFM) to disrupt this crystallization and accelerate coagulation. We therefore performed a study with small, well-defined groups of patients to investigate whether these effects on A5 binding and activity are also detectable in plasmas from patients with the aPL syndrome. A5 binding to phospholipid was significantly reduced by plasmas of patients with the aPL syndrome and thromboembolism compared with healthy controls (mean +/- SD, 26.7 +/- 4.3 ng/well [n = 25] vs 30.5 +/- 3.1 ng/well [n = 20], P < .01) and the non-aPL thromboembolism group (29.9 +/- 3.2 ng/well [n = 15], P < .05). A5 anticoagulant activity was reduced by plasmas of patients with aPL syndrome and thromboembolism compared with aPL antibodies without thrombosis (182 +/- 31% [n = 25] vs 210 +/- 35% [n = 26], P < .01), non-aPL thromboembolism (229 +/- 16% [n = 15], P < .001), and healthy controls (231 +/- 14% [n = 30], P < .001). In conclusion, in accordance with recent AFM data with monoclonal human aPL antibodies, plasmas from patients with aPL antibodies with thromboembolism reduce both A5 binding to phospholipid and A5 anticoagulant activity. This "annexin A5 resistance" identifies a novel mechanism for thrombosis in the aPL syndrome.
Rand
Jacob H
JH
Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. jrand@montefiore.org
Wu
Xiao-Xuan
XX
Lapinski
Robert
R
van Heerde
Waander L
WL
Reutelingsperger
Chris P
CP
Chen
Pojen P
PP
Ortel
Thomas L
TL
D017304:Annexin A5 / Q000378:metabolism / Q000502:physiology*; D017152:Antibodies, Antiphospholipid / Q000097:blood / Q000502:physiology*; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000150:complications; D001777:Blood Coagulation; D016022:Case-Control Studies; D006801:Humans; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D013923:Thromboembolism / Q000097:blood / Q000209:etiology
D017304:Annexin A5; D017152:Antibodies, Antiphospholipid; D010743:Phospholipids