title: Genomic responses during acute human anaphylaxis are characterized by upregulation of innate inflammatory gene networks.
abstract: BACKGROUND
  Systemic spread of immune activation and mediator release is required for the development of anaphylaxis in humans. We hypothesized that peripheral blood leukocyte (PBL) activation plays a key role.
  
  
  OBJECTIVE
  To characterize PBL genomic responses during acute anaphylaxis.
  
  
  METHODS
  PBL samples were collected at three timepoints from six patients presenting to the Emergency Department (ED) with acute anaphylaxis and six healthy controls. Gene expression patterns were profiled on microarrays, differentially expressed genes were identified, and network analysis was employed to explore underlying mechanisms.
  
  
  RESULTS
  Patients presented with moderately severe anaphylaxis after oral aspirin (2), peanut (2), bee sting (1) and unknown cause (1). Two genes were differentially expressed in patients compared to controls at ED arrival, 67 genes at 1 hour post-arrival and 2,801 genes at 3 hours post-arrival. Network analysis demonstrated that three inflammatory modules were upregulated during anaphylaxis. Notably, these modules contained multiple hub genes, which are known to play a central role in the regulation of innate inflammatory responses. Bioinformatics analyses showed that the data were enriched for LPS-like and TNF activation signatures.
  
  
  CONCLUSIONS
  PBL genomic responses during human anaphylaxis are characterized by dynamic expression of innate inflammatory modules. Upregulation of these modules was observed in patients with different reaction triggers. Our findings indicate a role for innate immune pathways in the pathogenesis of human anaphylaxis, and the hub genes identified in this study represent logical candidates for follow-up studies.
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research and the University of Western Australia, Perth, Australia; Department of Emergency Medicine, Royal Perth Hospital, Perth, Australia.
authors.forename: Shelley F
authors.initials: SF
authors.lastname: Stone
authors.affiliation: Telethon Kids Institute and the Centre for Child Health Research, University of Western Australia, Perth, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bosco
authors.affiliation: Telethon Kids Institute and the Centre for Child Health Research, University of Western Australia, Perth, Australia.
authors.forename: Anya
authors.initials: A
authors.lastname: Jones
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research and the University of Western Australia, Perth, Australia; Department of Emergency Medicine, Royal Perth Hospital, Perth, Australia.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Cotterell
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research and the University of Western Australia, Perth, Australia; Department of Emergency Medicine, Royal Perth Hospital, Perth, Australia.
authors.forename: Pauline E
authors.initials: PE
authors.lastname: van Eeden
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research and the University of Western Australia, Perth, Australia; Department of Emergency Medicine, Royal Perth Hospital, Perth, Australia.
authors.forename: Glenn
authors.initials: G
authors.lastname: Arendts
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research and the University of Western Australia, Perth, Australia; Department of Emergency Medicine, Royal Perth Hospital, Perth, Australia.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Fatovich
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research and the University of Western Australia, Perth, Australia; Department of Emergency Medicine, Royal Perth Hospital, Perth, Australia.
authors.forename: Simon G A
authors.initials: SG
authors.lastname: Brown
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000707:Anaphylaxis / Q000378:metabolism*; D005260:Female; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D015854:Up-Regulation