title: Proteomic analysis reveals innate immune activity in intestinal transplant dysfunction.
abstract: BACKGROUND
  Many patients with intestinal failure require intestinal transplantation (ITx) to survive. Acute cellular rejection poses a challenge in ITx because its biologic components are incompletely understood. New methodologies for its integrative and longitudinal analysis are needed.
  
  
  METHODS
  In this study, we characterized episodes of acute cellular rejection in ITx recipients using a noninvasive proteomic analysis. Ostomy effluent was obtained from all patients undergoing ITx at University of California, Los Angeles from July 2008 to September 2009 during surveillance endoscopies in the first 8 weeks post-ITx. Effluent was analyzed using 17-plex Luminex technology and matrix-assisted laser desorption/ionization proteomics.
  
  
  RESULTS
  Of 56 ostomy effluent samples from 17 ITx recipients, 14% developed biopsy-proven rejection at a median of 25 days post-ITx. Six had mild rejection, two were indeterminate for rejection, and no graft loss was seen in the first 3 months posttransplantation. Effluent levels of five innate immune cytokines were elevated in the posttransplantation phase: granulocyte colony-stimulating factor, interleukin-8, tissue necrosis factor-α, interleukin-1β, and interferon-γ. Proteomic analysis revealed 17 protein features differentially seen in rejection, two identified as human neutrophil peptide 1 and 2. This was confirmed by the presence of human neutrophil peptide-positive lamina propria neutrophils in biopsy tissue samples.
  
  
  CONCLUSIONS
  Proteomic and cytokine analysis of ostomy effluents suggests an early and unappreciated role of innate immune activation during rejection.
authors.affiliation: Department of Pediatric Gastroenterology, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
authors.forename: Anjuli R
authors.initials: AR
authors.lastname: Kumar
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.forename: James F
authors.initials: JF
authors.lastname: Leblanc
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Farmer
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
authors.forename: David
authors.initials: D
authors.lastname: Ziring
mesh_terms: D000328:Adult; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004766:Enterostomy; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D040901:Proteomics / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023084:alpha-Defensins / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; D053583:Interleukin-1beta; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma