Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis

NCT05936333 | Recruiting

• 1 other identifier: APHP221169
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic histiocytic intervillositis (CHI) is a rare condition with an incidence of 5 in 10,000 pregnancies. This rare condition is associated with placental inflammatory lesions leading to severe and recurrent obstetrical complications: intrauterine growth retardation (IUGR), fetal death in utero and miscarriage. The pathophysiological mechanisms of CHI are poorly understood, while the empirical treatments prescribed to prevent recurrence are cumbersome and of poor efficacy. Recent findings suggest that an alloimmune response may play a role. In a recent work, the investigators have demonstrated the role of maternal alloantibodies directed against fetal HLA antigens in two patients followed for recurrent IUGR associated with CHI. Their work suggests that a humoral alloimmune response directed against fetal HLA antigens mimics an allograft rejection process. The investigators propose to extend the preliminary results obtained in these patients to provide new insights into the pathophysiological mechanisms of CHI, and eventually to predict the risks of fetal loss.

Conditions

Chronic Histiocytic Intervillositis; Intrauterine Growth Retardation; Fetal Death in Utero; Miscarriage

Outcome Measures

Primary Outcomes (1)

• Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology

  Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology, namely CD68+ infiltrate, AND C4d deposits on the trophoblastic villi AND the presence of at least one FSA (fetus-specific antibody, directed against fetal HLA antigens in the maternal blood) with an elevated level, defined by a Mean Fluorescence Intensity (MFI) \> 10,000). This proportion of patients observed in CHI carriers will be compared to the proportion of patients with the concomitant presence of the same 3 criteria observed in the other two control groups.

  up to 6 months

Secondary Outcomes (6)

• To measure the FSA levels by Mean Fluorescence Intensity for the different obstetrical complications: intrauterine growth retardation (IUGR), fetal death in utero and abortion for IUGR.

  up to 6 months

• to measure the correlation between fetus-specific antibody level by Mean Fluorescence Intensity and the severity and/or precocity of obstetrical complications

  up to 6 months

• measure of semi-quantitative graduation of C4d in placenta compared to percentage of villositis

  up to 6 months

• measure of semi-quantitative graduation of CD68+ infiltrate in placenta compared to surface and number of involved villositis

  up to 6 months

• To measure the expression of HLA class I and II molecules by placental villi by ß2-microglobulin and HLA-DR labelling

  up to 6 months

Study Arms (3)

Patient with chronic histiocytic intervillositis

EXPERIMENTAL

Patient with CHI, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection

Procedure: Biological collection

patients with anti-phospholipid syndromes (APS)

ACTIVE COMPARATOR

Patient with antiphospholipid syndrome, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection

Procedure: Biological collection

women with a third full-term pregnancy without growth retardation.

PLACEBO COMPARATOR

Patient with normal pregnancies, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection

Procedure: Biological collection

Interventions

Biological collection PROCEDURE

up to 25 mL of blood collection for the adults and saliva collection for the minor at inclusion, and placenta collection at childbirth

Patient with chronic histiocytic intervillositis; patients with anti-phospholipid syndromes (APS); women with a third full-term pregnancy without growth retardation.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mother and father ≥ 18 years old
• For mothers in the CHI group :
• History of a normal pregnancy (full term, alive child) or IUGR/MFIU or miscarriage(s) or abortion followed by at least 1 obstetrical complication such as IUGR, MFIU, miscarriage
• Diagnosis of chronic histiocytic intervillitis made by placental anatomopathological examination with CD68+ marking
• For the mothers of the antiphospholipid syndrom group
• History of miscarriage(s)
• Having an anti-phospholipid syndrome
• For mothers in the normal pregnancy group:
• Third consecutive pregnancy of normal course, at term (≥ 36 weeks of amenorrhea) with eutrophic child
• For the mother and father:
• o Consent to participate in the study and for the participation in the study of at least one child and/or the use of existing samples (placenta / fetal DNA) from at least one previous pregnancy with CHI for the CHI group or at least one previous miscarriage for the APS group
• For the father:
• o Father of the last pregnancy and of the child(ren) participating in the study
• Exlusion criteria :
• For mothers in the normal pregnancy group:

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Antoine Béclère Hospital

Clamart, France

RECRUITING

MeSH Terms

Conditions

Fetal Growth Retardation; Stillbirth; Abortion, Spontaneous

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fetal Death; Death

Study Officials

• Alexandra LETOURNEAU, Doctor

  APHP, Antoine Béclère Hospital, CLAMART, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexandra LETOURNEAU, Doctor

CONTACT

331 45 37 44 76; letourneau.alexandra@aphp.fr

Alexandra BENACHI, Professor

CONTACT

331 45 37 44 76; alexandra.benachi@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2023
• First Posted: July 7, 2023
• Study Start: October 11, 2023
• Primary Completion: October 11, 2025
• Study Completion: October 11, 2025
• Last Updated: November 6, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)