Presented in part at the 59th National Meeting of the American College of Rheumatology, San Francisco, CA, October 1995
Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti-β2-Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β2-Glycoprotein I and Induce Endothelial Activation†
Version of Record online: 12 DEC 2005
Copyright © 1997 American College of Rheumatology
Arthritis & Rheumatism
Volume 40, Issue 3, pages 551–561, March 1997
How to Cite
Papa, N. D., Guidali, L., Sala, A., Buccellati, C., Khamashta, M. A., Ichikawa, K., Koike, T., Balestrieri, G., Tincani, A., Hughes, G. R. V. and Meroni, P. L. (1997), Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti-β2-Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β2-Glycoprotein I and Induce Endothelial Activation. Arthritis & Rheumatism, 40: 551–561. doi: 10.1002/art.1780400322
- Issue online: 12 DEC 2005
- Version of Record online: 12 DEC 2005
- Manuscript Accepted: 9 SEP 1996
- Manuscript Received: 3 JUN 1996
- Regione Lombardia-piano 122
- Consiglio Nazionale Ricerche Progetto Strategico (Citochine: aree di intervento e strategie terapeutiche)
- Ministero Università Ricerche Scientifiche Technologie
Objective. To investigate the ability of human anti-β2-glycoprotein I (anti-β2GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions.
Methods. Six human affinity-purified polyclonal anti-β2GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphos-pholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent β2GPI and 2) modulate endothelial adhesion molecule expression and interleukin-6 (IL-6) and 6-keto-prostaglandin F1α (6-keto-PGF1α) secretion.
Results. The affinity-purified IgG and the MAb with anti-β2GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum-free medium and was restored in a dose-dependent manner by exogenous human β2GPI. After EC binding, both polyclonal and monoclonal antibodies up-regulated adhesion molecule expression. Anti-β2GPI MAb also significantly increased IL-6 and 6-keto-PGF1α secretion.
Conclusion. These findings support the hypothesis that anti-β2GPI antibodies bind and activate EC through the adherent cofactor β2GPI, likely leading to a procoagulant state.