title: Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology.
abstract: BACKGROUND
  High-density oligoarray technology is a novel method for screening the expression of thousands of genes in a small tissue sample. Oligoarray analysis of genes expressed during human renal allograft rejection has not been reported previously.
  
  
  METHODS
  Seven human renal allograft biopsies with histologic evidence of acute cellular rejection and three renal allograft biopsies without evidence of rejection (control) were analyzed for the expression of 6800 human genes using high-density oligoarrays (GeneChip, Affymetrix, Santa Clara, CA). Quantitative expression of gene transcripts was determined and a comparison analysis between acute rejection and control biopsy samples was performed. Up-regulation of a specific gene transcript during acute rejection was considered to be significant if transcript abundance increased fourfold or more relative to control biopsy samples.
  
  
  RESULTS
  Comparison analysis revealed that between 32 and 219 gene transcripts are up-regulated (>fourfold) during acute rejection. Of these transcripts, only four (human monokine induced by interferon-gamma, T-cell receptor active beta-chain protein, interleukin-2 stimulated phosphoprotein, and RING4 (a transporter involved in antigen presentation)) were consistently up-regulated in each acute rejection sample relative to at least two of three control biopsy samples. Six other genes were up-regulated in six of seven acute rejection samples. These were interferon-stimulated growth factor-3, complement factor 3, nicotinamide N-methyltransferase, macrophage inflammatory protein-3beta, myeloid differentiation protein, and CD18. Only two gene transcripts were down-regulated in five of seven acute rejection samples. Significant up-regulation of cytotoxic T-cell effector molecules, previously reported as markers of acute renal rejection in humans, was not detected.
  
  
  CONCLUSIONS
  High-density oligoarray technology is useful for screening gene expression in transplanted tissues undergoing acute rejection. Because this method does not rely on a priori knowledge of which genes are involved in acute rejection, it is likely to yield novel insights into the mechanisms and diagnosis of rejection.
authors.affiliation: Renal Division, Department of Medicine, Transplantation Section, Emory University, Atlanta, Georgia, USA.
authors.forename: E
authors.initials: E
authors.lastname: Akalin
authors.forename: R C
authors.initials: RC
authors.lastname: Hendrix
authors.forename: R G
authors.initials: RG
authors.lastname: Polavarapu
authors.forename: T C
authors.initials: TC
authors.lastname: Pearson
authors.forename: J F
authors.initials: JF
authors.lastname: Neylan
authors.forename: C P
authors.initials: CP
authors.lastname: Larsen
authors.forename: F G
authors.initials: FG
authors.lastname: Lakkis
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D054415:Chemokine CCL19; D054370:Chemokine CXCL9; D019742:Chemokines, CC / Q000235:genetics; D019743:Chemokines, CXC / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; C515460:CCL19 protein, human; C080810:CXCL9 protein, human; D054415:Chemokine CCL19; D054370:Chemokine CXCL9; D019742:Chemokines, CC; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; C073119:TAP1 protein, human