Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- 未提供
结局指标
主要结局
Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology
时间窗: 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.
次要结局
- 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.(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(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(up to 6 months)
- measure of semi-quantitative graduation of C4d in placenta compared to percentage of villositis(up to 6 months)
- Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin)(up to 6 months)
- measure of semi-quantitative graduation of CD68+ infiltrate in placenta compared to surface and number of involved villositis(up to 6 months)