TY - JOUR
T1 - Differential effects of anti-β2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome
AU - George, Jacob
AU - Blank, Miri
AU - Levy, Yair
AU - Meroni, Pierluigi
AU - Damianovich, Maya
AU - Tincani, Angela
AU - Shoenfeld, Yehuda
PY - 1998/3/10
Y1 - 1998/3/10
N2 - Background - The antiphospholipid syndrome (APS) entails a prothrombotic state associated with the presence of anticardiolipin antibodies (aCL). aCL were shown to promote endothelial cell and platelet activation and to induce an APS-like syndrome in mice when administered intravenously. Recent data suggest that aCL target the plasma cofactor β2-glycoprotein I (β2GPI] rather than negatively charged phospholipids. However, it has not been determined whether different epitope-specific anti-β2GPI antibodies obtained from one patient possess pathogenic properties. Methods and Results - Three β2GPI-binding IgM monoclonal antibodies (mAbs) (ILA-1, ILA-3, and ILA-4) were cloned from a patient with APS. The three antibodies were shown to bind β2GPI immobilized on irradiated plates, yet only ILA-1 bound β2GPI coated onto nonirradiated plates. Furthermore, when using the anti-β2GPI enzyme- linked immunosorbent assay, ILA-1 was the only mAb inhibited by fluid phase β2GPI. ILA-1 and ILA-3, but not ILA-4, induced adherence of U937 cells to endothelial cells in vitro (reflecting activation of endothelial cells). mAbs ILA-1 and ILA-3 as opposed to ILA-4 induced significant expression of adhesion molecules when preincubated with human umbilical vein endothelial cells. Passive administration of ILA-1 and ILA-3 to pregnant BALB/c mice induced clinical findings consistent with APS (increased fetal resorptions, reduced platelet counts, and prolonged activated partial thromboplastin time), whereas both ILA-4 and the control human IgM did not produce similar effects. Conclusions - The results of the study demonstrate the differential effects of various populations of anti-β2GPI antibodies on endothelial cell activation and on experimental APS.
AB - Background - The antiphospholipid syndrome (APS) entails a prothrombotic state associated with the presence of anticardiolipin antibodies (aCL). aCL were shown to promote endothelial cell and platelet activation and to induce an APS-like syndrome in mice when administered intravenously. Recent data suggest that aCL target the plasma cofactor β2-glycoprotein I (β2GPI] rather than negatively charged phospholipids. However, it has not been determined whether different epitope-specific anti-β2GPI antibodies obtained from one patient possess pathogenic properties. Methods and Results - Three β2GPI-binding IgM monoclonal antibodies (mAbs) (ILA-1, ILA-3, and ILA-4) were cloned from a patient with APS. The three antibodies were shown to bind β2GPI immobilized on irradiated plates, yet only ILA-1 bound β2GPI coated onto nonirradiated plates. Furthermore, when using the anti-β2GPI enzyme- linked immunosorbent assay, ILA-1 was the only mAb inhibited by fluid phase β2GPI. ILA-1 and ILA-3, but not ILA-4, induced adherence of U937 cells to endothelial cells in vitro (reflecting activation of endothelial cells). mAbs ILA-1 and ILA-3 as opposed to ILA-4 induced significant expression of adhesion molecules when preincubated with human umbilical vein endothelial cells. Passive administration of ILA-1 and ILA-3 to pregnant BALB/c mice induced clinical findings consistent with APS (increased fetal resorptions, reduced platelet counts, and prolonged activated partial thromboplastin time), whereas both ILA-4 and the control human IgM did not produce similar effects. Conclusions - The results of the study demonstrate the differential effects of various populations of anti-β2GPI antibodies on endothelial cell activation and on experimental APS.
KW - Adhesion molecules
KW - Antibodies
KW - Endothelium
KW - Immune system
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M3 - Article
C2 - 9521339
AN - SCOPUS:0032502289
VL - 97
SP - 900
EP - 906
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 9
ER -