Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis (RH-PL)

Assistance Publique - Hôpitaux de Paris

Status: Enrolling

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

Treatments: Procedure: Biological collection

Study type: Interventional

Funder types: Other

Identifiers

NCT05936333

APHP221169

Details and patient eligibility

About

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 3 patient groups, including a placebo group

Patient with chronic histiocytic intervillositis

Experimental group

Description:

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

Treatment:

Procedure: Biological collection

patients with anti-phospholipid syndromes (APS)

Active Comparator group

Description:

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

Treatment:

Procedure: Biological collection

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

Placebo Comparator group

Description:

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

Treatment:

Procedure: Biological collection