Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

Mother and father ≥ 18 years old

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

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biological collection

    Procedure/Surgery

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

Treatment groups

200 Participants
are divided into 3 treatment groups
Group A: Patient with chronic histiocytic intervillositisExperimental treatment 1 intervention
Group B: patients with anti-phospholipid syndromes (APS)Active comparator 1 intervention
Group C: women with a third full-term pregnancy without growth retardation.Placebo comparator 1 intervention

Trial outcomes

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.

Time frame
up to 6 months

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.