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INTERLEUKIN-10 AND POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER AFTER KIDNEY TRANSPLANTATION 1 SVEN ARVID BIRKELAND, 2 KLAUS BENDTZEN, 3 BJARNE MØLLER, 4 STEPHEN HAMILTON-DUTOIT, 5 AND HANS KERZEL ANDERSEN 6 Department of Nephrology and Tissue Culture Laboratory, Odense University Hospital, Odense; Institute for Inflammation Research, RHIMA Centre, Rigshospitalet, National Hospital, Copenhagen; and Department of Clinical Immunology, Institute of Pathology and Section for Virology, Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark Background. Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation, which comprises a morphologically and clinically heterogeneous spectrum of B-lympho- cyte diseases. Risk factors include primary or reacti- vated Epstein-Barr virus (EBV) infection, and the type and duration of immunosuppression. Interleukin-10 (IL-10) is a pleiotropic cytokine, produced primarily by T-helper 2 (Th2) lymphocytes in the later stages of T-cell activation, suggested to play a role in EBV-asso- ciated PTLD. We recently reported preliminary find- ings on IL-10 in relation to the development of PTLD in three kidney transplanted patients. The study now includes nine patients that could be followed before and/or after the occurrence of lymphoma. Methods. Nine patients with lymphomas (eight PTLDs and one Hodgkin’s disease) were diagnosed among 268 consecutive renal transplantations (1990 – 1997). All were treated with cyclosporine with an ini- tial 10-day course of antilymphocyte globulin, supple- mented from 1995 with mycophenolate mofetil. Serum antibodies against EBV were detected using recombi- nant antigens. A double sandwich enzyme-linked im- munosorbent assay using rabbit antibodies to purified human recombinant IL-10 was employed; the assay is specific for human natural and viral IL-10. Results. Three patients experienced primary EBV in- fection, five reactivated EBV infections, and one did not change EBV status. Three patients had a fulminant course and died with EBV-associated PTLD confirmed post mortem. The other six are alive and are apparently cured. Treatment was immediate discontinuation of im- munosuppression (in all PTLDs) and long-term high- dose aciclovir in all but one. Two patients have main- tained excellent graft function for 3 and 2 years, respectively, without immunosuppression and are now in a state of operational tolerance. In three of four cases with initial lymphoma, EBV infection (primary or reac- tivation) preceded the increase in IL-10. In all four cases, the IL-10 increase preceded the PTLD diagnosis. In six cases, IL-10 could be followed after treatment showing either immediate zero or a decrease to zero. 1 This work was supported by the European Commission, Direc- torate General XII, BIOMed 2 contract BMH4-CT96-0610 Cancer After Transplantation (EURO-CAT), the Danish Kidney Foundation, and the Danish Biotechnology Program. 2 Department of Nephrology and Tissue Culture Laboratory, Odense University Hospital. 3 Institute for Inflammation Research, RHIMA Centre, Rigshos- pitalet, National Hospital, Copenhagen. 4 Department of Clinical Immunology, Aarhus University Hospital. 5 Institute of Pathology, Aarhus University Hospital. 6 Section for Virology, Department of Clinical Microbiology, Aar- hus University Hospital. TRANSPLANTATION 876 Vol. 67, No. 6