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Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

Raman K, Wang H, Troncone MJ, Khan WI, Pare G, Terry J - PLoS ONE (2015)

Bottom Line: Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth.IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue.These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Proportions of IgA, IgM, and IgG expressing plasma cells in oCPI-related CD compared to isolated CD.Error bars represent the 95% confidence interval of the mean.
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pone.0133738.g006: Proportions of IgA, IgM, and IgG expressing plasma cells in oCPI-related CD compared to isolated CD.Error bars represent the 95% confidence interval of the mean.

Mentions: We identified IgJ protein expression by immunohistochemistry in plasma cells in areas of oCPI related VUE (Fig 4A) and CD (Fig 4B). Since IgJ comprises part of the secretory immunoglobulin IgA and the expression profile associated with oCPI includes genes related to hollow viscus immunity, we surmised a potential connection between oCPI and IgA. To investigate this further, we subclassified CD-associated plasma cells by immunohistochemistry with respect to IgA, IgM, and IgG expression. IgA positive plasma cells were present in oCPI-related CD whereas they appeared to be absent in isolated CD (i.e. without histological evidence of VUE and/or chronic chorioamnionitis) (Fig 5). This difference was confirmed by quantification of IgA, IgM, and IgG expressing plasma cells which revealed that approximately 10% of plasma cells in oCPI-related CD express IgA compared to an absence of IgA-positive plasma cells in isolated CD (Fig 6). Levels of IgG and IgM-positive plasma cells were similar in both oCPI and isolated CD.


Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

Raman K, Wang H, Troncone MJ, Khan WI, Pare G, Terry J - PLoS ONE (2015)

Proportions of IgA, IgM, and IgG expressing plasma cells in oCPI-related CD compared to isolated CD.Error bars represent the 95% confidence interval of the mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514672&req=5

pone.0133738.g006: Proportions of IgA, IgM, and IgG expressing plasma cells in oCPI-related CD compared to isolated CD.Error bars represent the 95% confidence interval of the mean.
Mentions: We identified IgJ protein expression by immunohistochemistry in plasma cells in areas of oCPI related VUE (Fig 4A) and CD (Fig 4B). Since IgJ comprises part of the secretory immunoglobulin IgA and the expression profile associated with oCPI includes genes related to hollow viscus immunity, we surmised a potential connection between oCPI and IgA. To investigate this further, we subclassified CD-associated plasma cells by immunohistochemistry with respect to IgA, IgM, and IgG expression. IgA positive plasma cells were present in oCPI-related CD whereas they appeared to be absent in isolated CD (i.e. without histological evidence of VUE and/or chronic chorioamnionitis) (Fig 5). This difference was confirmed by quantification of IgA, IgM, and IgG expressing plasma cells which revealed that approximately 10% of plasma cells in oCPI-related CD express IgA compared to an absence of IgA-positive plasma cells in isolated CD (Fig 6). Levels of IgG and IgM-positive plasma cells were similar in both oCPI and isolated CD.

Bottom Line: Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth.IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue.These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus