title: Acute appendicitis: transcript profiling of blood identifies promising biomarkers and potential underlying processes.
abstract: The diagnosis of acute appendicitis can be surprisingly difficult without computed tomography, which carries significant radiation exposure. Circulating blood cells may carry informative changes in their RNA expression profile that would signal internal infection or inflammation of the appendix.
  
  
  
  Genome-wide expression profiling was applied to whole blood RNA of acute appendicitis patients versus patients with other abdominal disorders, in order to identify biomarkers of appendicitis. From a large cohort of emergency patients, a discovery set of patients with surgically confirmed appendicitis, or abdominal pain from other causes, was identified. RNA from whole blood was profiled by microarrays, and RNA levels were filtered by a combined fold-change (>2) and p value (<0.05). A separate set of patients, including patients with respiratory infections, was used to validate a partial least squares discriminant (PLSD) prediction model.
  
  
  
  Transcript profiling identified 37 differentially expressed genes (DEG) in appendicitis versus abdominal pain patients. The DEG list contained 3 major ontologies: infection-related, inflammation-related, and ribosomal processing. Appendicitis patients had lower level of neutrophil defensin mRNA (DEFA1,3), but higher levels of alkaline phosphatase (ALPL) and interleukin-8 receptor-ß (CXCR2/IL8RB), which was confirmed in a larger cohort of 60 patients using droplet digital PCR (ddPCR).
  
  
  
  Patients with acute appendicitis have detectable changes in the mRNA expression levels of factors related to neutrophil innate defense systems. The low defensin mRNA levels suggest that appendicitis patient's immune cells are not directly activated by pathogens, but are primed by diffusible factors in the microenvironment of the infection. The detected biomarkers are consistent with prior evidence that biofilm-forming bacteria in the appendix may be an important factor in appendicitis.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA.|The Department of Medicine, Veterans Affairs Medical Center, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA.
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.affiliation: Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Toma
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Davison
authors.affiliation: Department of Surgery, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA.
authors.forename: Khashayar
authors.initials: K
authors.lastname: Vaziri
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA.|Department of Surgery, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA.
authors.forename: Juliet
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, The George Washington University Medical School and GW Medical Faculty Associates, Washington, DC, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lucas
authors.affiliation: Department of Emergency Medicine, The George Washington University Medical School and GW Medical Faculty Associates, Washington, DC, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Seneff
authors.affiliation: Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA.
authors.forename: Aoibhinn
authors.initials: A
authors.lastname: Nyhan
authors.affiliation: Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA. mcc@gwu.edu.|Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA. mcc@gwu.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McCaffrey
mesh_terms: D000208:Acute Disease; D000328:Adult; D001064:Appendicitis / Q000097:blood* / Q000000981:diagnostic imaging / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D019295:Computational Biology / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers
keywords: Alkaline phosphatase; Appendicitis; Biomarkers; Defensin; Interleukin-8 receptor; Transcript profiling