Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell-Mediated Rejection

Am J Transplant. 2015 Oct;15(10):2718-25. doi: 10.1111/ajt.13304. Epub 2015 May 18.

Abstract

Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell-mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell-mediated rejection characteristics of both groups were similar at baseline. The expression of RORγt, Il-17 and T-bet mRNA was significantly higher in the elderly than in the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA levels were significantly higher in elderly patients experiencing successful acute T cell-mediated rejection reversal (p = 0.03). The presence of IL-17 mRNA was strongly associated with nonsuccessful reversal in elderly patients (p = 0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3 expression experienced significantly more treatment failure (87.5%) than patients with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p = 0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and prognosis of acute T cell-mediated rejection in recipients of expanded criteria allograft.

Keywords: Biomarker; donors and donation: extended criteria; molecular biology: mRNA/mRNA expression; rejection: T cell-mediated (TCMR).

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Allografts / immunology*
  • Allografts / metabolism
  • Allografts / pathology
  • Biomarkers / metabolism
  • Biopsy
  • Donor Selection*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Graft Rejection / immunology*
  • Graft Rejection / metabolism
  • Graft Rejection / pathology
  • Humans
  • Interleukin-17 / metabolism
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Transplantation, Homologous

Substances

  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17