Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome
| Autor: | Nina P. Rios-Luna, Gabriela Cesarman-Maus, Arunkumar B. Deora, Donato Alarcon-Segovia, Maria del Carmen Cravioto, Katherine A. Hajjar, Rosario Villa, Bihui Huang, Jorge Sanchez-Guerrero |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Plasmin Immunology Biochemistry Hemostasis Thrombosis and Vascular Biology Immunoglobulin G Thromboplastin Antigen Antiphospholipid syndrome Pregnancy Internal medicine medicine Beta 2-Glycoprotein I Humans Fibrinolysin Annexin A2 Aged Autoantibodies Aged 80 and over Immunoassay Systemic lupus erythematosus biology business.industry Endothelial Cells Thrombosis Cell Biology Hematology Middle Aged medicine.disease Antiphospholipid Syndrome Pregnancy Complications Endocrinology Case-Control Studies biology.protein Female Endothelium Vascular business Fibrinolytic agent medicine.drug |
| Zdroj: | Blood. 107(11) |
| ISSN: | 0006-4971 |
| Popis: | 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 β2-glycoprotein I (β2GPI), 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 tPAdependent generation assay (19%-71%) independently of β2GPI, 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. |
| Databáze: | OpenAIRE |
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