title: Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.
abstract: Breakdown of the balance between maternal pro- and anti-inflammatory pathways is thought to allow an anti-fetal maternal immune response that underlies development of chronic placental inflammation. Chronic placental inflammation is manifested by the influx of maternal inflammatory cells, including lymphocytes, histiocytes, and plasma cells, into the placental membranes, villi, and decidua. These infiltrates are recognized pathologically as chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth. Studying the gene expression patterns in chronically inflamed placenta, particularly when overlapping histologies are present, may lead to a better understanding of the underlying mechanism(s). Therefore, this study compared tissue with and without chronic placental inflammation, manifested as overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. RNA expression profiling was conducted on formalin fixed, paraffin embedded placental tissue using Illumina microarrays. IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue. In addition, IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the inflamed placental samples. These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells. Furthermore, these genes differ from those typically associated with the individual components of chronic placental inflammation, such as chronic villitis, suggesting that the inflammatory infiltrate associated with overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis differs is unique. To further explore and validate gene expression findings, we conducted immunohistochemical assessment of protein level expression and demonstrate that IgJ expression was largely attributable to the presence of plasma cells as part of chronic deciduitis and that IgA positive plasma cells are associated with chronic deciduitis occurring in combination with chronic chorioamnionitis and chronic villitis of unknown etiology but not with isolated chronic deciduitis.
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kripa
authors.initials: K
authors.lastname: Raman
authors.affiliation: Farncombe Family Digestive Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology and Molecular Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Troncone
authors.affiliation: Farncombe Family Digestive Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Waliul I
authors.initials: WI
authors.lastname: Khan
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; Farncombe Family Digestive Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.affiliation: Department of Pathology and Molecular Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Terry
mesh_terms: D002821:Chorioamnionitis / Q000235:genetics* / Q000473:pathology; D002824:Chorionic Villi / Q000378:metabolism / Q000473:pathology*; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D046228:Microarray Analysis; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D010922:Placenta Diseases / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D007136:Immunoglobulins