Journal Article

Immunohistochemical characterization of glomerular and tubulointerstitial infiltrates in renal transplant patients with chronic allograft dysfunction

Chiara Divella, Michele Rossini, Antonia Loverre, Antonio Schena, Annamaria Maiorano, Vincenzo Gesualdo, Gianluigi Zaza, Giuseppe Grandaliano and Francesco Paolo Schena

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 25, issue 12, pages 4071-4077
Published in print December 2010 | ISSN: 0931-0509
Published online June 2010 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfq377
Immunohistochemical characterization of glomerular and tubulointerstitial infiltrates in renal transplant patients with chronic allograft dysfunction

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Background. The term chronic allograft nephropathy (CAN) was deleted in the Eighth Banff Classification and two new categories were introduced: chronic T-cell-mediated rejection (CTMR) and chronic active humoral rejection (CAHR). The aim of this study was to revise our CAN cases diagnosed in the last 4 years, analyse allograft survival rates and identify types of infiltrating cells in the different settings.

Methods. Seventy-nine patients with biopsy-proven CAN were examined and classified into four groups according to the Banff 2005 criteria: CTMR, CAHR, chronic calcineurin inhibitor toxicity (CNITOX) and interstitial fibrosis and tubular atrophy not otherwise specified (NOS). CD4, CD8, CD20, CD68, CD103, Foxp3 and IL-17 protein expression and C4d deposits were investigated.

Results. We diagnosed 20 CTMR, 13 CAHR, 28 CNITOX, and 18 NOS. Death-censored graft survival at 4 years from renal biopsy was worse in CAHR compared with the other types of chronic injury. Glomerular CD8+ cells were increased in CTMR vs CNITOX and NOS. Interstitial CD4+ and CD8+ cells were increased in CTMR vs CNITOX. CD68+ cells in glomerular and peritubular capillaries were higher in CAHR vs CNITOX, CTMR and NOS. CD103+ cells were higher in cases with tubulitis than in those without. T regulatory and T helper 17 cells were rarely observed in the different settings.

Conclusions. Graft survival was worse in patients with CAHR. The presence of any grade transplant glomerulopathy and chronic allograft vasculopathy are poorer prognostic factors. Infiltrating CD8+, CD103+ and CD4+ cells may help to differentiate CTMR from other types of chronic injury, thus improving diagnostic/prognostic features of biopsy in patients with chronic allograft dysfunction.

Keywords: Banff schema; chronic active antibody-mediated rejection; chronic T-cell-mediated rejection; immunohistochemical markers; renal transplantation

Journal Article.  4329 words.  Illustrated.

Subjects: Nephrology

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