title: The peripheral whole-blood transcriptome of acute pyelonephritis in human pregnancya.
abstract: OBJECTIVE
  Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection for the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis.
  
  
  METHODS
  A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analyses were applied.
  
  
  RESULTS
  A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were upregulated and 526 were downregulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included (a) cytokine-cytokine receptor interaction, (b) T-cell receptor signaling, (c) Jak-STAT signaling, and (d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression.
  
  
  CONCLUSIONS
  This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is associated with the increased expression of genes involved in innate immunity and the decreased expression of genes involved in lymphocyte function.
authors.forename: Ichchha
authors.initials: I
authors.lastname: Madan
authors.forename: Nandor Gabor
authors.initials: NG
authors.lastname: Than
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.forename: Jezid
authors.initials: J
authors.lastname: Miranda
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bhatti
authors.forename: Sorin
authors.initials: S
authors.lastname: Draghici
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Moshe
authors.initials: M
authors.lastname: Mazor
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016014:Linear Models; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000235:genetics* / Q000276:immunology; D011704:Pyelonephritis / Q000097:blood / Q000235:genetics* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D015854:Up-Regulation; D055815:Young Adult