title: Chronic inflammation of the placenta: definition, classification, pathogenesis, and clinical significance.
abstract: Chronic inflammatory lesions of the placenta are characterized by the infiltration of the organ by lymphocytes, plasma cells, and/or macrophages and may result from infections (viral, bacterial, parasitic) or be of immune origin (maternal anti-fetal rejection). The 3 major lesions are villitis (when the inflammatory process affects the villous tree), chronic chorioamnionitis (which affects the chorioamniotic membranes), and chronic deciduitis (which involves the decidua basalis). Maternal cellular infiltration is a common feature of the lesions. Villitis of unknown etiology (VUE) is a destructive villous inflammatory lesion that is characterized by the infiltration of maternal T cells (CD8+ cytotoxic T cells) into chorionic villi. Migration of maternal T cells into the villi is driven by the production of T-cell chemokines in the affected villi. Activation of macrophages in the villi has been implicated in the destruction of the villous architecture. VUE has been reported in association with preterm and term fetal growth restriction, preeclampsia, fetal death, and preterm labor. Infants whose placentas have VUE are at risk for death and abnormal neurodevelopmental outcome at the age of 2 years. Chronic chorioamnionitis is the most common lesion in late spontaneous preterm birth and is characterized by the infiltration of maternal CD8+ T cells into the chorioamniotic membranes. These cytotoxic T cells can induce trophoblast apoptosis and damage the fetal membranes. The lesion frequently is accompanied by VUE. Chronic deciduitis consists of the presence of lymphocytes or plasma cells in the basal plate of the placenta. This lesion is more common in pregnancies that result from egg donation and has been reported in a subset of patients with premature labor. Chronic placental inflammatory lesions can be due to maternal anti-fetal rejection, a process associated with the development of a novel form of fetal systemic inflammatory response. The syndrome is characterized by an elevation of the fetal plasma T-cell chemokine. The evidence that maternal anti-fetal rejection underlies the pathogenesis of many chronic inflammatory lesions of the placenta is reviewed. This article includes figures and histologic examples of all chronic inflammatory lesions of the placenta.
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, and Detroit, MI.
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI. Electronic address: romeror@mail.nih.gov.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, and Detroit, MI; Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Kim
mesh_terms: D018414:CD8-Positive T-Lymphocytes; D018925:Chemokines; D002821:Chorioamnionitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D002824:Chorionic Villi / Q000473:pathology*; D002908:Chronic Disease; D003656:Decidua / Q000473:pathology*; D005260:Female; D054502:Histocompatibility, Maternal-Fetal; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008264:Macrophages; D010950:Plasma Cells; D011247:Pregnancy
chemical_list: D018925:Chemokines
keywords: C4d; CD8; CXCL10; HLA; T cell; VUE; allograft; chemokine; chronic chorioamnionitis; chronic deciduitis; complement; fetal death; fetal growth restriction; maternal floor infarction; plasma cells; prematurity; rejection; tolerance