Anti-tissue transglutaminase antibodies bind to trophoblast cells and promote apoptosis: can contribute to gynecoobstetric complications of celiac disease ?

SÓÑORA C, MOURGLIA G, HERNÁNDEZ A, HAUK V, RAMHORST R, PÉREZ LEIRÓS C.

Granada

Congreso; 8th. International Congress on Autoimmuninity; 2012

Celiac disease is often associated with impaired pregnancy. Antibodies against Tissue transglutaminase (tTG) developed during disease could be involved in pathogenic mechanisms since tTG has multiple functions at maternal-fetal interface; it is involved in both apoptosis and clearance of apoptotic cells, two main events often deregulated in pregnancy complications. We proposed to analyze if autoantibodies could affect apoptosis of trophoblastic cells. trophoblastic cultures (Swan 71) were used to evaluate the effect of antibodies on apoptosis. Flow Cytometry and western blot were used to verify tTG expression with reference antibody (tTG-MoAb) and the binding of antibodies from patients. Apoptosis was induced by depletion of fetal bovine serum (24 hours). The antibodies effect on apoptosis rate was evaluated in parallel with tTG-MoAb (25μg/ml) and sera dilutions from celiac women with gyneco-obstetric complications and from healthy donors as control group. Apoptosis was quantified by Annexin V-FITC /Propidium Iodide staining. Anti- tTG MoAb and sera from celiac patients showed significant binding so surface trophoblastic cells and western blot analysis revealed tTG specific recognition. Incubation of cells with anti-tTG MoAb induced a 2.7 fold increase of apoptotic cells in comparison with basal apoptosis while the effect of celiac sera ranged from 0.7-2.9 (median 1.7), with three sera showing similar effect than MoAb at comparable protein content of control sera. Results show that some celiac sera have a significant synergic effect on the apoptosis induced by protein deprivation. It is feasible that depending on fine specificity, a proapoptotic effect of autoantibodies could contribute to impaired implantation.