Clinical trial NCT05936333: Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis
Official title: Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Histiocytic Intervillositis
Intrauterine Growth Retardation
Fetal Death in Utero
Miscarriage
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-07-07
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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)

Primary outcomes:
measure: Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology
timeFrame: up to 6 months
Secondary outcomes:
measure: 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.
timeFrame: up to 6 months
measure: to measure the correlation between fetus-specific antibody level by Mean Fluorescence Intensity and the severity and/or precocity of obstetrical complications
timeFrame: up to 6 months
measure: measure of semi-quantitative graduation of C4d in placenta compared to percentage of villositis
timeFrame: up to 6 months
measure: measure of semi-quantitative graduation of CD68+ infiltrate in placenta compared to surface and number of involved villositis
timeFrame: up to 6 months
measure: To measure the expression of HLA class I and II molecules by placental villi by ß2-microglobulin and HLA-DR labelling
timeFrame: up to 6 months
measure: Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin)
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Clamart
country: France
facility: Antoine Béclère Hospital
Study officials:
affiliation: APHP, Antoine Béclère Hospital, CLAMART, France
name: Alexandra LETOURNEAU, Doctor
role: PRINCIPAL_INVESTIGATOR
References: