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. 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 beta2GPI and the catalytic domains of disease-relevant 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 APSpatients. 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. 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 APSpatients recognize one or more conformational epitopes shared by beta2GPI and the catalytic domains of disease-relevant serine proteases.
Authors: W A Wilson; A E Gharavi; T Koike; M D Lockshin; D W Branch; J C Piette; R Brey; R Derksen; E N Harris; G R Hughes; D A Triplett; M A Khamashta Journal: Arthritis Rheum Date: 1999-07
Authors: Fosca A F Di Prima; Oriana Valenti; Entela Hyseni; Elsa Giorgio; Marianna Faraci; Eliana Renda; Roberta De Domenico; Santo Monte Journal: J Prenat Med Date: 2011-04
Authors: M Anthony Moody; Hua-Xin Liao; S Munir Alam; Richard M Scearce; M Kelly Plonk; Daniel M Kozink; Mark S Drinker; Ruijun Zhang; Shi-Mao Xia; Laura L Sutherland; Georgia D Tomaras; Ian P Giles; John C Kappes; Christina Ochsenbauer-Jambor; Tara G Edmonds; Melina Soares; Gustavo Barbero; Donald N Forthal; Gary Landucci; Connie Chang; Steven W King; Anita Kavlie; Thomas N Denny; Kwan-Ki Hwang; Pojen P Chen; Philip E Thorpe; David C Montefiori; Barton F Haynes Journal: J Exp Med Date: 2010-04-05 Impact factor: 14.307
Authors: Zurina Romay-Penabad; Maria Guadalupe Montiel-Manzano; Tuya Shilagard; Elizabeth Papalardo; Gracie Vargas; Arun B Deora; Michael Wang; Andrew T Jacovina; Ethel Garcia-Latorre; Elba Reyes-Maldonado; Katherine A Hajjar; Silvia S Pierangeli Journal: Blood Date: 2009-07-23 Impact factor: 22.113