Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Biological collection.
- Who it may be relevant to
- Registry conditions: Chronic Histiocytic Intervillositis, Intrauterine Growth Retardation, Fetal Death in Utero, Miscarriage. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- Procedure Biological collection
up to 25 mL of blood collection for the adults and saliva collection for the minor at inclusion, and placenta collection at childbirth
Primary outcome measures
- 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]
Secondary outcome measures (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. [Time frame: 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 [Time frame: up to 6 months]
- measure of semi-quantitative graduation of C4d in placenta compared to percentage of villositis [Time frame: up to 6 months]
- measure of semi-quantitative graduation of CD68+ infiltrate in placenta compared to surface and number of involved villositis [Time frame: 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 [Time frame: up to 6 months]
- Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin) [Time frame: up to 6 months]
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)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Basic science
Study locations
France · 1 center
- Antoine Béclère Hospital — Clamart
Identifiers
NCT: NCT05936333 · APHP221169