Study of the Role of Tissular Maternofetal Alloimmunization in Placentation Pathologies

Justification: We have recently demonstrated that maternofetal alloimmunization was not limited to blood cells: maternal alloimmunization against a glomerular podocyte antigen expressed by the placenta can induce neonatal membranous glomerulonephritis. Early recurrent pregnancy losses, preeclampsia and intervillositis are obstetrical pathologies which share an anomaly of placentation. Pathophysiology of these diseases is not yet fully understood; nevertheless the hypothesis of an incompatibility between mother and child is often mentioned. The aim of this project is to detect and study the cases of recurrent pregnancy losses, preeclamspia and intervillositis which could be induced by tissular maternofetal alloimmunization. Materials and methods: Patients suffering from recurrent pregnancy losses of unknown origin, preeclamspia or intervillositis will be included in this project. Mothers' sera will be studied by indirect immunofluorescence and Western Blot on placental biopsies from different origins and gestational ages. This stage will enable us to detect possible maternal allo-antibodies. After detecting and revealing antibodies, nature of the target antigen will be identified by immunoprecipitation of placental extracts, using the positive sera. Immunoprecipitation will be followed by a mass spectrometry analysis of detected proteins. Expected results: This study will enable us:

• to detect new cases of tissular maternofetal alloimmunization
• to improve our knowledge of mechanisms leading to anomalies of placentation
• to carry out a specific, preventive therapeutic approach for cases induced by tissular alloimmunization. Key words: Recurrent pregnancy losses, Preeclampsia, Intervillositis, maternofetal alloimmunization.