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.

Study Overview

• Status: Completed
• Conditions: Preeclampsia; Recurrent Pregnancy Losses; Intervillositis

• Study Type: Observational
• Enrollment (Actual): 83

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Bordeaux university hospital
  • Limoges, France, 87042
    • Limoges university hospital
  • Paris, France, 75020
    • Tenon Hospital
  • Paris, France, 75012
    • Saint Antoine Hospital
  • Paris, France, 75571
    • Trousseau Hospital
  • Saint Pierre, France, 97448
    • South Reunion Hospital
  • Toulouse, France, 31059
    • Toulouse University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Neonatal pathologies can be caused by an alloimmunisation maternal fetal tissue, it's conceivable that certain pathologies. Obstetrics may be part of the same mechanism. Among these pathologies placentaires, for whom a "maternal-fetal incompatibility" is often mentioned, could be secondary to tissue alloimmunization against antigens independent of the immune system

Description

Inclusion Criteria:

• Recurrent pregnancy losses : patient having or having suffered from at least 3 consecutive, unexplained recurrent pregnancy losses, during the first 3 months of pregnancy, with the same paerson/man.
• Preeclampsia : blood pressure > 140/90 mm Hg ; proteinuria > 0,3 g/ 24 h
• Intervillositis : patient suffering or having suffered from intervillositis

Exclusion Criteria:

• Recurrent pregnancy losses : uterine pathology, endocrine pathology, autoimmune pathology, coagulation and hemostasis pathology, karyotype anomaly.
• Preeclampsia : pre-existing high blood pressure, pre-existing diabetes, pre-existing renal disease, antiphospholipid antibodies syndrome
• Intervillositis : intervillositis with villositis

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
repeated miscarriages; 60 womens for repeated miscarriages will be included
Preeclampsia; 70 women for pre-eclampsia will be included
intervillites; 20 women for intervillites will be included

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: April 3, 2007
• First Submitted That Met QC Criteria: April 3, 2007
• First Posted (Estimate): April 4, 2007

Study Record Updates

• Last Update Posted (Actual): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 10, 2018
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: preeclampsia; recurrent pregnancy losses; intervillositis; maternofetal alloimmunization
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia
• Other Study ID Numbers: I06014