Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome.
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 (beta2GPI), 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 nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies. Anti-A2 antibodies (titer > 3 SDs) 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 < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001). Anti-A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold +/- 0.13-fold SE), blocked A2-supported plasmin generation in a tPA-dependent generation assay (19%-71%) independently of beta2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%. We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome.
Cesarman-Maus
Gabriela
G
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY, USA. gcesarman@gmail.com
Ríos-Luna
Nina P
NP
Deora
Arunkumar B
AB
Huang
Bihui
B
Villa
Rosario
R
Cravioto
Maria del Carmen
Mdel C
Alarcón-Segovia
Donato
D
Sánchez-Guerrero
Jorge
J
Hajjar
Katherine A
KA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000209:etiology* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications; D013925:Thromboplastin / Q000096:biosynthesis; D013927:Thrombosis / Q000209:etiology
C472822:ANXA2 protein, human; D017306:Annexin A2; D001323:Autoantibodies; D013925:Thromboplastin; D005341:Fibrinolysin