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  • Alloimmune responses and atherosclerotic disease after kidney transplantation.

Alloimmune responses and atherosclerotic disease after kidney transplantation.

Transplantation (2014-10-07)
Didier Ducloux, Cécile Courivaud, Jamal Bamoulid, Vincent Bisaccia, Caroline Roubiou, Thomas Crepin, Béatrice Gaugler, Caroline Laheurte, Jean-Michel Rebibou, Jean-Marc Chalopin, Philippe Saas
ABSTRACT

Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. 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. 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; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=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; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P<0.0001). Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Azathioprine, ≥98%
Supelco
Azathioprine, Pharmaceutical Secondary Standard; Certified Reference Material
Mycophenolate mofetil, European Pharmacopoeia (EP) Reference Standard
USP
Mycophenolate mofetil, United States Pharmacopeia (USP) Reference Standard
USP
Azathioprine, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Mycophenolate mofetil, ≥98% (HPLC)
Azathioprine, European Pharmacopoeia (EP) Reference Standard
Supelco
Mycophenolate Mofetil, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
(±)-CPP, solid
Ciclosporin, European Pharmacopoeia (EP) Reference Standard
Mycophenolate mofetil for peak identification, European Pharmacopoeia (EP) Reference Standard