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Kidney Int. 2016 May;89(5):1136-1143. doi: 10.1016/j.kint.2015.12.044. Epub 2016 Mar 2.

Pretransplant thymic function predicts acute rejection in antithymocyte globulin-treated renal transplant recipients.

Author information

1
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.
2
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.
3
Department of Nephrology, Dialysis, and Renal Transplantation, CHU Besançon, Besançon, France; CHU Besançon, CIC Biothérapie, INSERM CIC1431, Besançon, France.
4
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.
5
INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, CIC 1431/UMR1098, Besançon, France.
6
Department of Nephrology, Dialysis, and Renal Transplantation, CHU Strasbourg, Strasbourg, France.
7
Department of Nephrology, Dialysis, and Renal Transplantation, CHU Nancy, Nancy, France.
8
Department of Nephrology, Dialysis, and Renal Transplantation, CHU Reims, Reims, France.
9
Department of Nephrology, Dialysis, and Renal Transplantation, CHU Dijon, Dijon, France.
10
Department of Nephrology, Dialysis, and Renal Transplantation, CHU Kremlin-Bicêtre, Le Kremlin-Bicêtre, France.
11
Department of Nephrology, Dialysis, and Renal Transplantation, CHU Clermont-Ferrand, Clermont-Ferrand, France.
12
INSERM, UMR1098, Federation hospitalo-universitaire INCREASE, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, CHU Dijon, Dijon, France.
13
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.
14
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.

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.

KEYWORDS:

CMV; acute graft rejection; immune senescence; thymus; transplantation

PMID:
27083287
DOI:
10.1016/j.kint.2015.12.044
[Indexed for MEDLINE]

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