Abstract 1337: Beta2GPI-Dependent aPL React with Endometrial/Decidual Cells and Affect Their Function: Study with Inhibitory Molecules
Authors
M. O. Borghi, E. Raschi, S. Scurati, C. Grossi, P. P. Chen, S. S. Pierangeli, P. L. Meroni
Background
One of the proposed mechanism for anti-phospholipid antibody (APL)-mediated fetal loss is antibody-associated placental thrombosis. Whether these mechanisms are targeting the fetal or maternal placental surface is a matter of debate.
Methods
The binding of APL (polyclonal IgG from patients, purified IgG, and anti-2GP1 monoclonal antibodies) to human endometrial and stromal cells was examined, and expression of adhesion molecules and proinflammatory cytokines measured. A specific peptide inhibitor of 2GP1 antibody, as well as blocking antibodies to Annexin 2 and TLR4 were used as well to study whether the effects of antibody on these cells can be reversed in vitro.
Results
All of the APL fractions and monoclonal antibodies tested bound to endometrial cells, and caused an increase in both adhesion molecule and proinflammatory cytokine expression by these cells. The inhibitory peptide and antibodies were able to decrease both ICAM expression and TNF secretion in these assays.
Editorial Comment
Though APL-induced pregnancy loss is a well-described phenomenon, there are few ways to prevent its occurrence other thna the use of broad spectrum anti-coagulants and the putative TLR inhibitor hydroxychloroquine. This study suggests that a peptide inhibitor of 2GP1 antibodies might have promise as a more targeted therapy in this syndrome. It also might help explain the mechanism of action of Plaquenil, which could work by blocking TLR-mediated increases in both adhesion molecules and TNF secretion by endometrial cells.
