title: Polyclonal antithymocyte globulin and cardiovascular disease in kidney transplant recipients.
abstract: T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs.
authors: Integrated Center for Research in Inflammatory Diseases (UMR1098), French Institute of Health and Medical Research, University Hospital Federation, Besançon, France; French Federal Research Institute for Engineering for Cellular and Tissue Biology (IFR133), University of Franche-Comté, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, University Hospital of Besançon, Besançon, France; Clinical Investigation Centre-Integrated Biotherapeutics (CIC-BT 506), University Hospital of Besançon, Besançon, France; and dducloux@chu-besancon.fr.
authors: Didier
authors: D
authors: Ducloux
authors: Integrated Center for Research in Inflammatory Diseases (UMR1098), French Institute of Health and Medical Research, University Hospital Federation, Besançon, France; French Federal Research Institute for Engineering for Cellular and Tissue Biology (IFR133), University of Franche-Comté, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, University Hospital of Besançon, Besançon, France;
authors: Cécile
authors: C
authors: Courivaud
authors: Integrated Center for Research in Inflammatory Diseases (UMR1098), French Institute of Health and Medical Research, University Hospital Federation, Besançon, France; French Federal Research Institute for Engineering for Cellular and Tissue Biology (IFR133), University of Franche-Comté, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, University Hospital of Besançon, Besançon, France;
authors: Jamal
authors: J
authors: Bamoulid
authors: Integrated Center for Research in Inflammatory Diseases (UMR1098), French Institute of Health and Medical Research, University Hospital Federation, Besançon, France; French Federal Research Institute for Engineering for Cellular and Tissue Biology (IFR133), University of Franche-Comté, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, University Hospital of Besançon, Besançon, France;
authors: Thomas
authors: T
authors: Crepin
authors: Integrated Center for Research in Inflammatory Diseases (UMR1098), French Institute of Health and Medical Research, University Hospital Federation, Besançon, France; French Federal Research Institute for Engineering for Cellular and Tissue Biology (IFR133), University of Franche-Comté, Besançon, France; Department of Nephrology, Dialysis, and Renal Transplantation, University Hospital of Besançon, Besançon, France; Clinical Investigation Centre-Integrated Biotherapeutics (CIC-BT 506), University Hospital of Besançon, Besançon, France; and.
authors: Jean-Marc
authors: JM
authors: Chalopin
authors: Integrated Center for Research in Inflammatory Diseases (UMR1098), French Institute of Health and Medical Research, University Hospital Federation, Besançon, France; French Federal Research Institute for Engineering for Cellular and Tissue Biology (IFR133), University of Franche-Comté, Besançon, France; Clinical Investigation Centre-Integrated Biotherapeutics (CIC-BT 506), University Hospital of Besançon, Besançon, France; and Biomonitoring Platform, French Blood Service Bourgogne Franche-Comté, Clinical Investigation Centre-Integrated Biotherapeutics (CIC-BT 506), Besançon, France.
authors: Pierre
authors: P
authors: Tiberghien
authors: Integrated Center for Research in Inflammatory Diseases (UMR1098), French Institute of Health and Medical Research, University Hospital Federation, Besançon, France; French Federal Research Institute for Engineering for Cellular and Tissue Biology (IFR133), University of Franche-Comté, Besançon, France; Clinical Investigation Centre-Integrated Biotherapeutics (CIC-BT 506), University Hospital of Besançon, Besançon, France; and Biomonitoring Platform, French Blood Service Bourgogne Franche-Comté, Clinical Investigation Centre-Integrated Biotherapeutics (CIC-BT 506), Besançon, France.
authors: Philippe
authors: P
authors: Saas
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D050197:Atherosclerosis / Q000139:chemically induced* / Q000276:immunology / Q000401:mortality; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000961:Antilymphocyte Serum; D007155:Immunologic Factors