Detection of endothelial cell-reactive immunoglobulin in patients with anti-phospholipid antibodies.
Individuals with anti-phospholipid antibodies are at increased risk for the development of thrombosis and fetal loss. The pathogenesis of these syndromes is unknown, but may involve antibody-mediated alterations in endothelial cell coagulant activity. To address this possibility, we determined the incidence of endothelial cell-reactive antibodies in 76 patients whose plasma contained anti-phospholipid antibodies, but who had no clinically-evident immune disorder. Plasma from 47 patients deposited significantly more immunoglobulin on cultured endothelial cells than control plasma. Positive tests were more frequent in patients with a history of thrombosis than in those without (17/19 v 23/48; P = 0.004). However, we observed no correlation between immunoglobulin deposition on cardiolipin and endothelial cells by individual plasmas. Furthermore, endothelial cell reactivity was not diminished by adsorption of anti-cardiolipin antibodies from patient sera using liposomes. Immunoglobulin fractions prepared from 5/6 patient sera immunoprecipitated a approximately 70 kDa endothelial cell surface protein; 4/5 of these fractions also induced the release of von Willebrand factor from endothelial cells. These results demonstrate that plasma from many patients with anti-phospholipid antibodies, but no clinically-evident autoimmune disease, also contains endothelial cell-reactive antibodies. Detection of such antibodies might help identify individuals in this patient population at greatest risk for thrombosis.
McCrae
K R
KR
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
DeMichele
A
A
Samuels
P
P
Roth
D
D
Kuo
A
A
Meng
Q H
QH
Rauch
J
J
Cines
D B
DB
D000906:Antibodies / Q000032:analysis; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis*; D016682:Lupus Coagulation Inhibitor / Q000032:analysis; D010743:Phospholipids / Q000276:immunology; D012307:Risk Factors; D013927:Thrombosis / Q000276:immunology; D014841:von Willebrand Factor / Q000032:analysis
D000906:Antibodies; D002308:Cardiolipins; D007136:Immunoglobulins; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids; D014841:von Willebrand Factor