Some antiphospholipid antibodies recognize conformational epitopes shared by beta2-glycoprotein I and the homologous catalytic domains of several serine proteases.
OBJECTIVE
To test the hypothesis that some antiphospholipid antibodies (aPL) in patients with the antiphospholipid syndrome (APS) recognize a conformational epitope shared by beta2-glycoprotein I (beta2GPI; the major autoantigen for the antiphospholipid antibodies) and the homologous catalytic domains of several serine proteases (such as thrombin, activated protein C [APC], and plasmin) involved in hemostasis.


METHODS
We generated 4 new IgG monoclonal aPL (2 screened against beta2GPI, 1 against thrombin, and 1 against protein C) from 2 APS patients. The monoclonal antibodies (mAb) were analyzed for binding to beta2GPI, thrombin, APC, and plasmin, as well as for anticardiolipin antibody (aCL) activity. To demonstrate a shared epitope between beta2GPI and a serine protease, 1 mAb was studied by cross-inhibition analysis.


RESULTS
Both of the IgG anti-beta2GPI mAb bound to thrombin, APC, and plasmin. On the other hand, the 1 anti-thrombin mAb and the 1 anti-protein C mAb also bound to beta2GPI. Moreover, the binding of 1 cross-reactive mAb to beta2GPI was inhibited by alpha-thrombin (which contains only the catalytic domain of thrombin). All 4 mAb displayed aCL activity.


CONCLUSIONS
Taken together with the findings that some aCL bind to several serine proteases that participate in hemostasis and share homologous catalytic domains, these data demonstrate that some aCL in APS patients recognize one or more conformational epitopes shared by beta2GPI and the catalytic domains of disease-relevant serine proteases.
Lin
Wei-Shiang
WS
University of California, Los Angeles, CA 90095-1670, USA.
Chen
Pei-Chih
PC
Yang
Cheng-De
CD
Cho
EunJung
E
Hahn
Bevra H
BH
Grossman
Jennifer
J
Hwang
Kwan-Ki
KK
Chen
Pojen P
PP
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001779:Blood Coagulation Factors / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005341:Fibrinolysin / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology*; D013917:Thrombin / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology*
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D001779:Blood Coagulation Factors; D000939:Epitopes; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; C091963:activated protein C receptor; D053482:beta 2-Glycoprotein I; D012697:Serine Endopeptidases; D013917:Thrombin; D005341:Fibrinolysin