Functionally significant renal allograft rejection is defined by transcriptional criteria

Steven C. Hoffmann, Douglas A. Hale, David E. Kleiner, Roslyn B. Mannon, Robert L. Kampen, Lynn M. Jacobson, Linda C. Cendales, John J. Swanson, Bryan N. Becker, Allan D. Kirk

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Renal allograff acute cellular rejection (ACR) is a T-cell mediated disease that is diagnosed histologically. However, many normally functioning allografts have T-cell infiltrates and histological ACR, and many nonimmune processes cause allograft dysfunction. Thus, neither histological nor functional criteria are sufficient to establish a significant rejection, and the fundamental features of clinical rejection remain undefined. To differentiate allograft lymphocyte infiltration from clinically significant ACR, we compared renal biopsies from patients with ACR to patients with: sub-clinical rejection (SCR, stable function with histological rejection); no rejection; and nontransplanted kidneys. Biopsies were compared histologically and transcriptionally by RT-PCR for 72 relevant immune function genes. Neither the degree nor the composition of the infiltrate defined ACR. However, transcripts up-regulated during effector TH1 T-cell activation, most significantly the transcription factor T-bet, the effector receptor Fas ligand and the costimulation molecule CD152 clearly (p = 0.001) distinguished the patient categories. Transcripts from other genes were equivalently elevated in SCR and ACR, indicating their association with infiltration, not dysfunction. Clinically significant ACR is not defined solely by the magnitude nor composition of the infiltrate, but rather by the transcriptional activity of the infiltrating cells. Quantitative analysis of selected gene transcripts may enhance the clinical assessment of allografts.

Original languageEnglish (US)
Pages (from-to)573-581
Number of pages9
JournalAmerican Journal of Transplantation
Volume5
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Acute rejection
  • Real-time PCR
  • Renal allotransplantation
  • Sub-clinical rejection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Hoffmann, S. C., Hale, D. A., Kleiner, D. E., Mannon, R. B., Kampen, R. L., Jacobson, L. M., Cendales, L. C., Swanson, J. J., Becker, B. N., & Kirk, A. D. (2005). Functionally significant renal allograft rejection is defined by transcriptional criteria. American Journal of Transplantation, 5(3), 573-581. https://doi.org/10.1111/j.1600-6143.2005.00719.x