Interleukin-17 positive cells accumulate in renal allografts during acute rejection and are independent predictors of worse graft outcome

Transpl Int. 2011 Oct;24(10):1008-17. doi: 10.1111/j.1432-2277.2011.01302.x. Epub 2011 Jul 14.

Abstract

Interleukin-17 (IL-17) plays an important role in the regulation of cellular and humoral immune responses. Recent studies suggest a role for IL-17 in transplantation. Our study investigated whether quantifying IL-17(+) cells in renal transplant biopsies during acute rejection could have additional prognostic value for better stratifying patients at risk for nonresponsiveness to anti-rejection therapy and future graft dysfunction. Forty-nine renal biopsies with acute rejection were double immunostained and quantitatively analyzed for IL-17 and CD3 (IL-17(+) T-lymphocytes), tryptase (IL-17(+) mast cells) or CD15 (IL-17(+) neutrophils). Total IL-17(+) cell count correlated with total percentage of inflamed biopsy and estimated GFR during rejection. Most IL-17(+) cells were mast cells and neutrophils. We could hardly find any IL-17(+) T-lymphocytes. IL-17(+) mast cells correlated with interstitial fibrosis/tubular atrophy (IF/TA). None of the IL-17(+) cell counts had an additional prognostic value for response to anti-rejection treatment. Multivariate analysis correcting for C4d positivity and time from transplantation to biopsy showed that total IL-17(+) cell count independently predicts graft dysfunction at the last follow-up, which was validated in an independent cohort of 48 renal biopsies with acute rejection. We conclude that intragraft IL-17(+) cell count during acute allograft rejection could have an additional value for predicting late graft dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Female
  • Glomerular Filtration Rate
  • Graft Rejection
  • Humans
  • Immunohistochemistry / methods
  • Interleukin-17 / biosynthesis*
  • Kidney Transplantation / methods*
  • Male
  • Mast Cells / cytology*
  • Mast Cells / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Neutrophils / metabolism
  • Renal Insufficiency / therapy*
  • Treatment Outcome

Substances

  • Interleukin-17