Anti-tissue transglutaminase antibody inhibits apoptotic cell clearance by macrophages in pregnant NOD mice

SOÑORA C; MOURGLIA-ETTLIN G; CALO G; HAUK V; RAMHORST R; HERNANDEZ A; PÉREZ LEIRÓS C

JOURNAL OF REPRODUCTIVE IMMUNOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2014 vol. 103 p. 59 - 66

0165-0378

Autoimmunity is a feature of Celiac Disease (CD) with tissue transglutaminase (tTG) as a major autoantigen. A correlation between gyneco-obstetric disorders in CD patients and the presence of circulating antibodies anti-tTG that inhibited tTG activity was reported. Serum anti-tTG antibodies were detected in non obese diabetic (NOD) mouse model of type I insulin-dependent diabetes mellitus and Sjögren´s syndrome, two comorbid states with CD. Since pregnancy complications were described in NOD mice, we evaluated the ability of anti-tTG antibodies to affect the functions of tTG relevant to early pregnancy normal course like extracellular matrix assembling and apoptotic cell phagocytosis by macrophages. NOD mice showed circulating IgG antibodies against tTG that reduced tTG transamidating activity. Their titres decreased at early pregnancy and were able to bind to pregnant endometrium with a pattern similar to a reference anti-tTG monoclonal antibody. Particularly, anti-tTG antibody inhibited apoptotic cell phagocytosis by peritoneal macrophages from pregnant NOD mice that express the enzyme on surface. Evidence provided support a role for anti tTG antibodies through reduced transamidating activity and reduced apoptotic cell clearance by pregnant NOD mice macrophages.