title: Interleukin-17 positive cells accumulate in renal allografts during acute rejection and are independent predictors of worse graft outcome.
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.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands. u.yapici@amc.uva.nl
authors.forename: Ünsal
authors.initials: Ü
authors.lastname: Yapici
authors.forename: Jesper
authors.initials: J
authors.lastname: Kers
authors.forename: Fréderike J
authors.initials: FJ
authors.lastname: Bemelman
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Jaap W
authors.initials: JW
authors.lastname: Groothoff
authors.forename: Chris M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: Karlijn A M I
authors.initials: KA
authors.lastname: van Donselaar-van der Pant
authors.forename: Mirza M
authors.initials: MM
authors.lastname: Idu
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020381:Interleukin-17 / Q000096:biosynthesis*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009504:Neutrophils / Q000378:metabolism; D051437:Renal Insufficiency / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D020381:Interleukin-17