title: Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell-Mediated Rejection.
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.
authors.affiliation: APHP, Henri Mondor Hospital, Nephrology and Transplantation Department, Créteil, France.|UPEC, Inserm U955, Team 21, Créteil, France.|APHP, Henri Mondor Hospital, CIC biotherapy, Créteil, France.
authors.forename: M
authors.initials: M
authors.lastname: Matignon
authors.affiliation: UPEC, Inserm U955, Team 11, Créteil, France.
authors.forename: A
authors.initials: A
authors.lastname: Aissat
authors.affiliation: APHP, Henri-Mondor hospital, Public Health department and Clinical Research Unit (URC-Mondor), Créteil, France.|UPEC, LIC EA4393, Créteil, France.
authors.forename: F
authors.initials: F
authors.lastname: Canoui-Poitrine
authors.affiliation: UPEC, Inserm U955, Team 21, Créteil, France.|APHP, Henri Mondor Hospital, CIC biotherapy, Créteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Grondin
authors.affiliation: UPEC, Inserm U955, Team 21, Créteil, France.|APHP, Henri Mondor Hospital, CIC biotherapy, Créteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Pilon
authors.affiliation: UPEC, Inserm U955, Team 21, Créteil, France.|Anatomopathology Department, APHP, Henri Mondor Hospital, Créteil, France.
authors.forename: D
authors.initials: D
authors.lastname: Desvaux
authors.affiliation: APHP, Pitié-Salpêtrière hospital, Internal Medicine and Immunology Department, Centre national de référence des Maladies Autoimmunes et systémiques rares, DHU I2B: Inflammation, Immunopathology, Biotherapy, Paris, France.|Laboratoire I3: Immunology-Immunopathology-Immunotherapeutique, UMR 7211 (UPMC/CNRS), U959 (INSERM), Pierre et Marie Curie University, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Saadoun
authors.affiliation: UPEC, Inserm U955, Team 21, Créteil, France.|APHP, Henri Mondor Hospital, CIC biotherapy, Créteil, France.
authors.forename: Q
authors.initials: Q
authors.lastname: Barathon
authors.affiliation: Laboratoire I3: Immunology-Immunopathology-Immunotherapeutique, UMR 7211 (UPMC/CNRS), U959 (INSERM), Pierre et Marie Curie University, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Garrido
authors.affiliation: APHP, Henri Mondor Hospital, Nephrology and Transplantation Department, Créteil, France.|UPEC, Inserm U955, Team 21, Créteil, France.|APHP, Henri Mondor Hospital, CIC biotherapy, Créteil, France.
authors.forename: V
authors.initials: V
authors.lastname: Audard
authors.affiliation: APHP, Henri Mondor Hospital, Nephrology and Transplantation Department, Créteil, France.|UPEC, Inserm U955, Team 21, Créteil, France.|APHP, Henri Mondor Hospital, CIC biotherapy, Créteil, France.
authors.forename: P
authors.initials: P
authors.lastname: Rémy
authors.affiliation: APHP, Henri Mondor Hospital, Nephrology and Transplantation Department, Créteil, France.|UPEC, Inserm U955, Team 21, Créteil, France.
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.affiliation: UPEC, Inserm U955, Team 21, Créteil, France.|APHP, Henri Mondor Hospital, CIC biotherapy, Créteil, France.
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.affiliation: APHP, Henri Mondor Hospital, Nephrology and Transplantation Department, Créteil, France.|UPEC, Inserm U955, Team 21, Créteil, France.|APHP, Henri Mondor Hospital, CIC biotherapy, Créteil, France.
authors.forename: P
authors.initials: P
authors.lastname: Grimbert
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D064591:Allografts / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D046148:Donor Selection; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17
keywords: Biomarker; donors and donation: extended criteria; molecular biology: mRNA/mRNA expression; rejection: T cell-mediated (TCMR)