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NCT Number: NCT05936333

Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis

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.

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Key information

Conditions

Chronic Histiocytic Intervillositis Abortion, Spontaneous Congenital, Hereditary, and Neonatal Diseases and Abnormalities Death Female Urogenital Diseases and Pregnancy Complications Fetal Death Fetal Death in Utero Fetal Diseases Fetal Growth Retardation Growth Disorders Intrauterine Growth Retardation Miscarriage Pathologic Processes Pathological Conditions, Signs and Symptoms Pregnancy Complications Stillbirth Urogenital Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Antoine Béclère Hospital

Clamart, France

Location status: Recruiting

Location contact

Alexandra BENACHI, Professor

CONTACT

Alexandra LETOURNEAU, Doctor

CONTACT

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Family Inclusion Criteria:

  • 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:

o Suspected or confirmed intra-amniotic infection

  • For all the mothers:
  • History of blood transfusion
  • History of allogeneic organ transplantation
  • For the mother and the father:
  • Person under legal protection (guardianship, curatorship)

Treatment and study plan

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

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

    Time frame: up to 6 months

    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.

Secondary outcomes

  1. 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.

    Time frame: up to 6 months

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

    Time frame: up to 6 months

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

    Time frame: up to 6 months

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

    Time frame: up to 6 months

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

    Time frame: up to 6 months

  6. Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin)

    Time frame: up to 6 months

    Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin) to determine whether an antibody response against a limited number of epitopes present during a first pregnancy that resulted in a healthy child can explain immunization against both paternal alleles

Study contacts

Contact information is provided by the study sponsor or research team.

Alexandra BENACHI, Professor

CONTACT

[email protected]

331 45 37 44 76

Alexandra LETOURNEAU, Doctor

CONTACT

[email protected]

331 45 37 44 76

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: RH-PL

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Jul 7, 2023
Registry last updated
Nov 6, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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