title: Pretransplant thymic function predicts acute rejection in antithymocyte globulin-treated renal transplant recipients.
abstract: Lack of clear identification of patients at high risk of acute rejection hampers the ability to individualize immunosuppressive therapy. Here we studied whether thymic function may predict acute rejection in antithymocyte globulin (ATG)-treated renal transplant recipients in 482 patients prospectively studied during the first year post-transplant of which 86 patients experienced acute rejection. Only CD45RA(+)CD31(+)CD4(+) T cell (recent thymic emigrant [RTE]) frequency (RTE%) was marginally associated with acute rejection in the whole population. This T-cell subset accounts for 26% of CD4(+) T cells. Pretransplant RTE% was significantly associated with acute rejection in ATG-treated patients (hazard ratio, 1.04; 95% confidence interval, 1.01-1.08) for each increased percent in RTE/CD4(+) T cells), but not in anti-CD25 monoclonal (αCD25 mAb)-treated patients. Acute rejection was significantly more frequent in ATG-treated patients with high pretransplant RTE% (31.2% vs. 16.4%) or absolute number of RTE/mm(3) (31.7 vs. 16.1). This difference was not found in αCD25 monclonal antibody-treated patients. Highest values of both RTE% (>31%, hazard ratio, 2.50; 95% confidence interval, 1.09-5.74) and RTE/mm(3) (>200/mm(3), hazard ratio, 3.71; 95% confidence interval, 1.59-8.70) were predictive of acute rejection in ATG-treated patients but not in patients having received αCD25 monoclonal antibody). Results were confirmed in a retrospective cohort using T-cell receptor excision circle levels as a marker of thymic function. Thus, pretransplant thymic function predicts acute rejection in ATG-treated patients.
authors.affiliation: INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; Faculté de Médecine et de Pharmacie, University Bourgogne Franche-Comté, Besançon, France; Structure Fédérative de Recherche, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France.
authors.forename: Jamal
authors.initials: J
authors.lastname: Bamoulid
authors.affiliation: INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; Faculté de Médecine et de Pharmacie, University Bourgogne Franche-Comté, Besançon, France; Structure Fédérative de Recherche, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Courivaud
authors.affiliation: INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; Faculté de Médecine et de Pharmacie, University Bourgogne Franche-Comté, Besançon, France; Structure Fédérative de Recherche, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Crepin
authors.affiliation: INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; Faculté de Médecine et de Pharmacie, University Bourgogne Franche-Comté, Besançon, France; Structure Fédérative de Recherche, Besançon, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Carron
authors.affiliation: Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France; CHU Besançon, CIC Biothérapie, INSERM CIC1431, Besançon, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Gaiffe
authors.affiliation: Faculté de Médecine et de Pharmacie, University Bourgogne Franche-Comté, Besançon, France; Structure Fédérative de Recherche, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Roubiou
authors.affiliation: INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, CIC 1431/UMR1098, Besançon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Laheurte
authors.affiliation: Department of Nephrology, Dialysis, and Renal Transplantation, CHU Strasbourg, Strasbourg, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
authors.affiliation: Department of Nephrology, Dialysis, and Renal Transplantation, CHU Nancy, Nancy, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Frimat
authors.affiliation: Department of Nephrology, Dialysis, and Renal Transplantation, CHU Reims, Reims, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rieu
authors.affiliation: Department of Nephrology, Dialysis, and Renal Transplantation, CHU Dijon, Dijon, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mousson
authors.affiliation: Department of Nephrology, Dialysis, and Renal Transplantation, CHU Kremlin-Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.affiliation: Department of Nephrology, Dialysis, and Renal Transplantation, CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Anne-Elisabeth
authors.initials: AE
authors.lastname: Heng
authors.affiliation: INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, CHU Dijon, Dijon, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rebibou
authors.affiliation: INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; Faculté de Médecine et de Pharmacie, University Bourgogne Franche-Comté, Besançon, France; Structure Fédérative de Recherche, Besançon, France; CHU Besançon, CIC Biothérapie, INSERM CIC1431, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, CIC 1431/UMR1098, Besançon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saas
authors.affiliation: INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; Faculté de Médecine et de Pharmacie, University Bourgogne Franche-Comté, Besançon, France; Structure Fédérative de Recherche, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France; CHU Besançon, CIC Biothérapie, INSERM CIC1431, Besançon, France. Electronic address: dducloux@chu-besancon.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Ducloux
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005602:France; D006084:Graft Rejection / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013950:Thymus Gland / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011948:Receptors, Antigen, T-Cell; C512542:thymoglobulin; D017493:Leukocyte Common Antigens
keywords: CMV; acute graft rejection; immune senescence; thymus; transplantation