Chronic histiocytic intervillositis: manifestation of placental alloantibody-mediated rejection
Chronic histiocytic intervillositis: manifestation of placental alloantibody-mediated rejection
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DOI：
10.1016/j.ajog.2021.06.051
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发表时间：
2021-11-27
影响因子：
9.8
通讯作者：
Zuber, Julien
中科院分区：
文献类型：
--
作者：
Benachi, Alexandra;Rabant, Marion;Zuber, Julien
背景技术背景：慢性组织细胞性绒毛间炎（慢性绒毛间炎）的定义是单核细胞弥漫性浸润到绒毛间隙，这通常会导致不良的产科结局，包括复发性宫内生长受限、流产和胎儿死亡。慢性绒毛间炎的发病机制仍然不明确，并且存在未满足的医疗需求，以改善management.Objective：本研究旨在通过应用实体器官移植中用于诊断抗体介导的排斥反应的标准来证明抗人类白细胞抗原同种抗体在慢性绒毛间炎发病机制中的作用。一项多学科的研究，基于彻底的免疫学和病理学调查进行了2个独立的夫妇谁经历了复发性继发性胎儿损失后，第一次正常妊娠与慢性绒毛间炎的组织学证据。结果：在这两种情况下，都发现了非常高水平的补体固定、胎儿特异性抗体，其靶向不匹配的人类白细胞抗原等位基因，这些等位基因由2个父亲单倍型所携带。多型人类白细胞抗原在炎症胎盘的滋养层绒毛表面表达，但在健康胎盘组织中不表达。同种抗体与父系人类白细胞抗原的结合诱导滋养层绒毛中补体经典途径的显著激活，导致C4d沉积和ter-binding复合物C5 b-9的形成。抗体介导的胎盘排斥反应的诊断的所有要求都符合移植物病理学的Banff分类标准。使用人类白细胞抗原表位查看器进行计算机模拟分析，以重建人类白细胞抗原致敏史。对第一个出生的健康儿童中存在的单个错配表位的反应性导致对人类白细胞抗原的广泛致敏，包括由2个父亲单倍型所携带的抗原。这一发现解释了慢性绒毛间炎复发率高，在随后的pregnances.CONCLUSION：这项研究提供了新的机制的见解慢性绒毛间炎的发病机制，并提供了个性化的咨询和治疗方案的新途径。
BACKGROUND: Chronic histiocytic intervillositis (chronic inter-villositis) is defined by a diffuse infiltration of monocytes into the intervillous space, which often leads to poor obstetrical outcomes, including recurrent intrauterine growth restriction, miscarriage, and fetal death. The patho-genesis of chronic intervillositis is still poorly defined, and there is an unmet medical need for improved management.OBJECTIVE: This study aimed to demonstrate the role of anti-human leukocyte antigen alloantibodies in the pathogenesis of chronic inter-villositis through the application of criteria used in solid-organ trans-plantation for the diagnosis of antibody-mediated rejection.STUDY DESIGN: A multidisciplinary research study based on thorough immunologic and pathologic investigations was carried out for 2 separate couples who experienced recurrent secondary fetal losses following a first normal pregnancy associated with histologic evidence of chronic intervillositis.RESULTS: Very high levels of complement-fixing, fetus-specific an-tibodies targeting mismatched human leukocyte antigen alleles, harbored by the 2 paternal haplotypes, were identified in both cases. Polymorphic human leukocyte antigens were expressed on the surface of trophoblastic villi of the inflamed placenta but not in healthy placental tissue. The binding of alloantibodies to paternal human leukocyte anti-gens induced dramatic activation of the complement classical pathway in trophoblastic villi, leading to C4d deposition and formation of the ter-minal complex C5b-9. All requirements for the diagnosis of antibody-mediated placental rejection were fulfilled according to the criteria used in the Banff classification of allograft pathology. In silico analysis was performed using a human leukocyte antigen epitope viewer to reconstitute the human leukocyte antigen sensitization history. Reactivity against a single mismatched epitope present in the first-born healthy child accounted for a broad sensitization to human leukocyte antigens, including those harbored by the 2 paternal haplotypes. This finding explained the high rates of chronic intervillositis recurrence during subsequent pregnancies.CONCLUSION: This study provides novel mechanistic insights into the pathogenesis of chronic intervillositis and provides new avenues for individualized counseling and therapeutic options.