Pro-inflammatory response estimulated by anti-β2 glycoprotein-i antibodies in trophoblast cells and monocytes-macrophages is associated with differences in tissue transglutaminase variants expression

ARBILDI P, GRASSO E, RODRÍGUEZ-CAMEJO C, PÉREZ-LEIRÓS C, RAMHORST R, HERNÁNDEZ A AND SÓÑORA C.

Uruguay

Simposio; Reunión anual de la Sociedad de Inmunología Uruguya, Instituto Pasteur,; 2016

Sociedad Uruguaya de Inmunología

Background:Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized bysignificant pregnancy morbidity. Beta 2 glycoprotein I (β2GPI) is constitutivelyexpressed by placental trophoblast and antibodies recognizing β2GPI are involved inobstetric disorders associated with APS by inducing a robust inflammatory response introphoblast .Tissue transglutaminase (TG2) is a multifunctional protein whose crosslinking activityregulates NF-kB signaling and inflammatory effects; TG2 truncated variants encodedby alternatively spliced mRNA transcripts are considered to be involved in TG2regulation.We analyzed the effects of anti- β2GPI on : i. proinflammatory cytokine production bytrophoblast cells and monocytes/macrophages and ii. expression of TG2 isoforms inthese cells involved in the maternal-fetal interface.Methods:Serum samples were obtained from women with APS and from fertile non-pregnantwomen as control.Trophoblast Swan-71 and PMA treated THP-1 cell lines were used to evaluate β2GPIantibodies effect on cytokine production by ELISA and TG2 variants expression byqPCR.Results:Sera with β2GPI antibodies significant increase trophoblast IL-6 production and alsoinduces TG2 expression in these cells in a dose dependent effect.In differentiated THP-1 cells β2GPI antibodies displayed a significant and dosedependent increase in IL-1 and IL-6 production and sera with β2GPI antibodiesinduces changes in expression of truncated isoforms of TG2.Conclusions:These results support β2GPI-specific antibodies effects on inflammation induction atmaternal-fetal interface and innovatively suggest that modulation of TG2 variantsexpression plays a role in this process. Further work is currently underway to deciphermolecular mechanisms underlying this regulation.