Alloimmune Responses and Atherosclerotic Disease After Kidney Transplantation. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Bisaccia, Vincent; Roubiou, Caroline; Crepin, Thomas; Gaugler, Béatrice; Laheurte, Caroline; Rebibou, Jean-Michel; Chalopin, Jean-Marc; Saas, Philippe
• Is Part Of: Transplantation. Volume 99:Issue 1(2015)
• Publication Date: 2015-01
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000000346
• Languages: English
• ISSNs: 0041-1337

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background</title> <p>Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57<sup>+</sup>CD28<sup>−</sup> hyperactivated CD8<sup>+</sup> T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis.</p> </sec> <sec> <title>Methods</title> <p>This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients.</p> </sec> <sec> <title>Results</title> <p>Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5–6, 3–4, and 0–2 mismatches, respectively; <italic>P</italic>=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10–1.66, for each supplementary mismatch; <italic>P</italic>=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05–0.95; <italic>P</italic>=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57<sup>+</sup>CD28<sup>−</sup> CD8<sup>+</sup> T cells (R=0.31; <italic>P</italic>=0.017). These CD8<sup>+</sup> T cells were more frequent in patients with more HLA mismatches (<italic>P</italic><0.0001).</p> </sec> <sec> <title>Conclusion</title> <p>Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.</p> </sec> </abstract>