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      No Effect of Transfusion Transmitted Virus Viremia on the Distribution and Activation of Peripheral Lymphocytes in Hemodialyzed Patients

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          Aim: We aimed to examine the distribution and activation of peripheral T cells in TTV positive (n = 32) and negative (n = 17) hemodialyzed patients. The control group (n = 20) consisted of healthy blood donors. Method: TTV-DNA was detected by seminested PCR. CD3, CD4, CD8, CD19, CD56, CD3/HLA-DR, CD3/CD69 and the Th1/Th2 ratio of T cells were analyzed by flow cytometry. Circulating IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-13, TNF-α, TGF-β levels were measured by ELISA in the sera. Results: There was no difference between the CD3, CD4, CD8 and CD19 values of HD subjects. In addition, the expression of both activation markers, HLA-DR and CD69, was significantly elevated in the TTV-positive and -negative HD groups compared to the controls, but not showing any difference from each other. The measurements of intracellular cytokines showed the enhanced occurrence of INF-γ + CD4 T cells, and decreased appearance of IL-4 + CD4 lymphocytes in the HD groups without any significant difference between the TTV virus positive and negative patients. In addition, HD also elevated the expression of IL-10 in CD4 and CD8 (Th2) cells. There were only two significant changes in the levels of circulating cytokines: (a) IL-2 increased; (b) IL-13 decreased in both groups of HD patients compared to the controls, independently of TTV positvity or negativity. Conclusions: We assume that transfusion-transmitted virus does not cause any specific change in the distribution and activation of lymphocytes in the peripheral blood of hemodialyzed patients. Hemodialysis itself, however, results in a significant activation of peripheral T cells with the domination of increased production of Th1 type cytokines, IFN-γ, IL-2, in contrast to the decreased synthesis of Th2 type cytokines, IL-4 and IL-13. Furthermore, the increased expression of IL-10 in the CD4 and CD8 cells of HD patients can be the sign of a contraregulatory Th2 activation as an answer on the Th1 effect.

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          Most cited references 16

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          A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology.

          By means of representational difference analysis, a viral clone (N22) of 500 nucleotides was isolated from serum of a patient (TT) with posttransfusion hepatitis of unknown etiology. The N22 clone showed a poor homology to any reported sequences. Oligonucleotide primers were deduced from the N22 sequence for detecting it by polymerase chain reaction. N22 sequence in serum banded at a sucrose density of 1.26 g/cm3, indicating its association with a viral particle which was designated TT virus (TTV). Since nucleic acids of TTV were sensitive to DNase I, it would be a DNA virus. TTV DNA was detected in sera from three of the five patients with posttransfusion non-A to G hepatitis, including the index case (TT). TTV DNA titers closely correlated with aminotransferase levels in the three patients. These results indicate that TTV would be a novel DNA virus with a possible capacity to induce posttransfusion non-A to G hepatitis. Copyright 1997 Academic Press.
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            Molecular cloning and characterization of a novel DNA virus (TTV) associated with posttransfusion hepatitis of unknown etiology

             H Okamoto (1998)
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              Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A-G hepatitis.

               Y Akahane,  M Ukita,  F Tsuda (1998)
              Five patients with type B or C hepatocellular carcinoma were found to be infected with a nonenveloped DNA virus (TTV) associated with posttransfusion hepatitis of non-A-G etiology. Paired feces and serum samples from these patients were tested for TTV DNA by polymerase chain reaction with seminested primers and their sequences were compared. TTV DNA was detected in sera from all of the patients, while it was detected in feces from three patients, including two with high viral titers in serum. When feces and serum from one patient were subjected to floatation ultracentrifugation in CsCl, TTV in feces banded at a peak density of 1.35 g/cm3 and that in serum at 1.31-1.32 g/cm3. TTV isolates in three pairs of feces and serum had the identical sequence of 222 base pairs. The excretion of TTV into feces indicates that TTV would be transmitted not only parenterally but also nonparenterally by a fecal-oral route.

                Author and article information

                S. Karger AG
                October 2002
                18 October 2002
                : 92
                : 4
                : 933-937
                aFMC Nephrology Center, Miskolc; b3rd Department of Medicine, Center of Medicine and Health Sciences, University of Debrecen; cDepartment of Virology of the National Health Center, Budapest; dMagyar-Med Dialysis Station, St Margaret Hospital, Budapest; eFMC Dialysis Station, Ózd; fFMC Dialysis Station, Sátoraljaújhely; gSemmelweis University, Department of Transplantation, Budapest, Hungary
                65449 Nephron 2002;92:933–937
                © 2002 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 2, References: 29, Pages: 5
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                Short Communication

                Cardiovascular Medicine, Nephrology

                TTV, Hemodialysis, Lymphocytes, Cytokines


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