title: Comparison of whole blood and peripheral blood mononuclear cell gene expression for evaluation of the perioperative inflammatory response in patients with advanced heart failure.
abstract: BACKGROUND
  Heart failure (HF) prevalence is increasing in the United States. Mechanical Circulatory Support (MCS) therapy is an option for Advanced HF (AdHF) patients. Perioperatively, multiorgan dysfunction (MOD) is linked to the effects of device implantation, augmented by preexisting HF. Early recognition of MOD allows for better diagnosis, treatment, and risk prediction. Gene expression profiling (GEP) was used to evaluate clinical phenotypes of peripheral blood mononuclear cells (PBMC) transcriptomes obtained from patients' blood samples. Whole blood (WB) samples are clinically more feasible, but their performance in comparison to PBMC samples has not been determined.
  
  
  METHODS
  We collected blood samples from 31 HF patients (57±15 years old) undergoing cardiothoracic surgery and 7 healthy age-matched controls, between 2010 and 2011, at a single institution. WB and PBMC samples were collected at a single timepoint postoperatively (median day 8 postoperatively) (25-75% IQR 7-14 days) and subjected to Illumina single color Human BeadChip HT12 v4 whole genome expression array analysis. The Sequential Organ Failure Assessment (SOFA) score was used to characterize the severity of MOD into low (≤ 4 points), intermediate (5-11), and high (≥ 12) risk categories correlating with GEP.
  
  
  RESULTS
  Results indicate that the direction of change in GEP of individuals with MOD as compared to controls is similar when determined from PBMC versus WB. The main enriched terms by Gene Ontology (GO) analysis included those involved in the inflammatory response, apoptosis, and other stress response related pathways. The data revealed 35 significant GO categories and 26 pathways overlapping between PBMC and WB. Additionally, class prediction using machine learning tools demonstrated that the subset of significant genes shared by PBMC and WB are sufficient to train as a predictor separating the SOFA groups.
  
  
  CONCLUSIONS
  GEP analysis of WB has the potential to become a clinical tool for immune-monitoring in patients with MOD.
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Galyna
authors.initials: G
authors.lastname: Bondar
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Martin
authors.initials: M
authors.lastname: Cadeiras
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wisniewski
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Jetrina
authors.initials: J
authors.lastname: Maque
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Jay
authors.initials: J
authors.lastname: Chittoor
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Chang
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Maral
authors.initials: M
authors.lastname: Bakir
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Starling
authors.affiliation: Columbia University, New York, NY, United States of America; East Carolina University, Greenville, NC, United States of America.
authors.forename: Khurram
authors.initials: K
authors.lastname: Shahzad
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Peipei
authors.initials: P
authors.lastname: Ping
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America.
authors.forename: Elaine
authors.initials: E
authors.lastname: Reed
authors.affiliation: University of California Los Angeles, Los Angeles, CA, United States of America; Columbia University, New York, NY, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Deng
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D006333:Heart Failure / Q000097:blood* / Q000601:surgery*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D059035:Perioperative Period / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger