From the Research Unit of Autoimmune Diseases (J.G., M.B., Y.L., M.D.,
Y.S., S.C.), Department of Medicine B Sheba Medical Center, Tel Hashomer,
Sackler Faculty of Medicine, Tel-Aviv University, Israel; IRCCS Policlinico,
Milan, Italy (P.M.); and Clinical Immunology Unit (A.T.), Spedali Civili,
Brescia, Italy.
Correspondence to Yehuda Shoenfeld, MD, Department of Medicine B, Sheba Medical Center, Tel-Hashomer, 52621, Israel. E-mail shoenfel{at}post.tau.il
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 ß2-glycoprotein I (ß2GPI)
rather than negatively charged phospholipids. However, it has not been
determined whether different epitope-specific anti-ß2GPI antibodies
obtained from one patient possess pathogenic properties.
Methods and Results—Three ß2GPI-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 ß2GPI immobilized
on irradiated plates, yet only ILA-1 bound ß2GPI coated onto
nonirradiated plates. Furthermore, when using the anti-ß2GPI
enzyme-linked immunosorbent assay, ILA-1 was the only mAb inhibited by
fluid phase ß2GPI. 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-ß2GPI antibodies on
endothelial cell activation and on experimental APS.
© 1998 American Heart Association, Inc.
Basic Science Reports
Differential Effects of Anti–ß2-Glycoprotein I Antibodies on Endothelial Cells and on the Manifestations of Experimental Antiphospholipid Syndrome
Key Words: endothelium • adhesion molecules • antibodies • immune system
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