Some antiphospholipid antibodies recognize conformational epitopes shared by β2-glycoprotein I and the homologous catalytic domains of several serine proteases
✍ Scribed by Wei-Shiang Lin; Pei-Chih Chen; Cheng-De Yang; EunJung Cho; Bevra H. Hahn; Jennifer Grossman; Kwan-Ki Hwang; Pojen P. Chen
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 120 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
Abstract
Objective
To test the hypothesis that some antiphospholipid antibodies (aPL) in patients with the antiphospholipid syndrome (APS) recognize a conformational epitope shared by β~2~‐glycoprotein I (β~2~GPI; 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 β~2~GPI, 1 against thrombin, and 1 against protein C) from 2 APS patients. The monoclonal antibodies (mAb) were analyzed for binding to β~2~GPI, thrombin, APC, and plasmin, as well as for anticardiolipin antibody (aCL) activity. To demonstrate a shared epitope between β~2~GPI and a serine protease, 1 mAb was studied by cross‐inhibition analysis.
Results
Both of the IgG anti‐β~2~GPI 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 β~2~GPI. Moreover, the binding of 1 cross‐reactive mAb to β~2~GPI was inhibited by α‐thrombin (which contains only the catalytic domain of thrombin). All 4 mAb displayed aCL activity.
Conclusion
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 β~2~GPI and the catalytic domains of disease‐relevant serine proteases.