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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4375-4382.
Prepublished online as a Blood First Edition Paper on February 21, 2006; DOI 10.1182/blood-2005-07-2636.
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Submitted July 5, 2005
Accepted January 20, 2006
Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome
Gabriela Cesarman-Maus*, Nina P Rios-Luna, Arunkumar B Deora, Bihui Huang, Rosario Villa, Maria del Carmen Cravioto, Donato Alarcon-Segovia, Jorge Sanchez-Guerrero, and Katherine A Hajjar
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, NY, NY, USA; Departments of Hematology, Immunology and Rheumatology and Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMNSZ), Mexico City, Mexico
Departments of Hematology, Immunology and Rheumatology and Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMNSZ), Mexico City, Mexico
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, NY, NY, USA
* Corresponding author; email: gcesarman{at}gmail.com.
The association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and beta-2-glycoprotein-I, the main antigen for antiphospholipid antibodies. Here we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with non-autoimmune thrombosis, and 145 healthy individuals) were analyzed by ELISA and immunoblot for antiphospholipid and anti-A2 antibodies (anti-A2Ab). Anti-A2Ab (titer >3SD) were significantly more prevalent in patients with APS (22.6%, venous 17.5%, arterial 34.3% and mixed thrombosis 40.4%), than in healthy individuals (2.1%, p< 0.001), patients with non-autoimmune thrombosis (0%, p=0.017) or patients with lupus without thrombosis (6.3%, p< 0.001). Anti-A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4 fold ± 0.13 SE), blocked A2-supported plasmin generation in a tPA-dependent generation assay (19-71%) independently of beta-2-glycoprotein-I, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECS) by 34-83%. We propose that anti-A2Ab contribute to the prothrombotic diathesis in antiphospholipid syndrome.
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