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Choice of Antibody Immunotherapy Influences Cytomegalovirus Viremia in Simultaneous Pancreas-Kidney Transplant Recipients

¹ Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
² Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands
³ Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
⁴ Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands

Address correspondence and reprint requests to Johan W. de Fijter, MD, PhD, Department of Nephrology, C3-22, Leiden University Medical Center, P.O. Box 9600, NL-2300 RC Leiden, Netherlands. E-mail: j.w.de_fijter{at}lumc.nl

OBJECTIVE—Simultaneous pancreas-kidney (SPK) transplantation in type 1 diabetic patients requires immunotherapy against allo- and autoreactive T-cells. Cytomegalovirus (CMV) infection is a major cause for morbidity after transplantation and is possibly related to recurrent autoimmunity. In this study, we assessed the pattern of CMV viremia in SPK transplant recipients receiving either antithymocyte globulin (ATG) or anti-CD25 (daclizumab) immunosuppressive induction therapy.

RESEARCH DESIGN AND METHODS—We evaluated 36 SPK transplant recipients from a randomized cohort that received either ATG or daclizumab as induction therapy. Patients at risk for CMV infection received oral prophylactic ganciclovir therapy. The CMV DNA level in plasma was measured for at least 180 days using a quantitative real-time PCR. Recipient peripheral blood mononuclear cells were cross-sectionally HLA tetramer-stained for CMV-specific CD8⁺ T-cells.

RESULTS—Positive CMV serostatus in donors was correlated with a higher incidence of CMV viremia than negative serostatus. In patients at risk, daclizumab induction therapy significantly prolonged CMV-free survival. CMV viremia occurred earlier and was more severe in patients with rejection episodes than in patients without rejection episodes. CMV-specific CD8⁺ T-cell counts were significantly lower in patients developing CMV viremia than in those who did not.

CONCLUSIONS—Despite their comparable immunosuppressive potential, daclizumab is safer than ATG regarding CMV infection risk in SPK transplantation. ATG-treated rejection episodes are associated with earlier and more severe infection. Furthermore, high CMV-specific tetramer counts reflect antiviral immunity rather than concurrent viremia because they imply low viremic activity. These findings may prove valuable in the discussion on both safety of induction therapy and recurrent autoimmunity in SPK and islet transplantation.

Abbreviations: ATG, antithymocyte globulin • ATG_F, ATG Fresenius • ATGM, ATG Merieux • CMV, cytomegalovirus • PBMC, peripheral blood mononuclear cell • SPK, simultaneous pancreas-kidney

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