title: Villitis of unknown etiology is associated with a distinct pattern of chemokine up-regulation in the feto-maternal and placental compartments: implications for conjoint maternal allograft rejection and maternal anti-fetal graft-versus-host disease.
abstract: The co-presence of histoincompatible fetal and maternal cells is a characteristic of human placental inflammation. Villitis of unknown etiology (VUE), a destructive inflammatory lesion of villous placenta, is characterized by participation of Hofbauer cells (placental macrophages) and maternal T cells. In contrast to acute chorioamnionitis of infection-related origin, the fundamental immunopathology of VUE is unknown. This study was performed to investigate the placental transcriptome of VUE and to determine whether VUE is associated with systemic maternal and/or fetal inflammatory response(s). Comparison of the transcriptome between term placentas without and with VUE revealed differential expression of 206 genes associated with pathways related to immune response. The mRNA expression of a subset of chemokines and their receptors (CXCL9, CXCL10, CXCL11, CXCL13, CCL4, CCL5, CXCR3, CCR5) was higher in VUE placentas than in normal placentas (p < 0.05). Analysis of blood cell mRNA showed a higher expression of CXCL9 and CXCL13 in the mother, and CXCL11 and CXCL13 in the fetus of VUE cases (p < 0.05). The median concentrations of CXCL9, CXCL10, and CXCL11 in maternal and fetal plasma were higher in VUE (p < 0.05). Comparison of preterm cases without and with acute chorioamnionitis revealed elevated CXCL9, CXCL10, CXCL11, and CXCL13 concentrations in fetal plasma (p < 0.05), but not in maternal plasma with chorioamnionitis. We report for the first time the placental transcriptome of VUE. A systemic derangement of CXC chemokines in maternal and fetal circulation distinguishes VUE from acute chorioamnionitis. We propose that VUE be a unique state combining maternal allograft rejection and maternal antifetal graft-vs-host disease mechanisms.
authors.affiliation: Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892 and Detroit, MI 48201, USA.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Sovantha
authors.initials: S
authors.lastname: Chhauy
authors.forename: Christopher
authors.initials: C
authors.lastname: LaJeunesse
authors.forename: Deug-Chan
authors.initials: DC
authors.lastname: Lee
authors.forename: Sorin
authors.initials: S
authors.lastname: Draghici
authors.forename: Francesca
authors.initials: F
authors.lastname: Gotsch
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Kim
mesh_terms: D018925:Chemokines / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D002821:Chorioamnionitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002824:Chorionic Villi / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005333:Fetus / Q000276:immunology*; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D008431:Maternal-Fetal Exchange / Q000235:genetics / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D010922:Placenta Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D019707:Receptors, Chemokine