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Studio del ruolo della viremia di torquetenovirus (TTV)come indicatore dello stato di immunosoppressione in pazienti trapiantati di midollo e/o di organo solido.

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Academic year: 2021

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Torque Teno virus (TTV) is the prototype of a group of extremely common viruses classified in the family of Anelloviridae. TTV is able to induce chronic viremia in approximately 80% of apparently healthy individuals and, once acquired, the infection may persist for years, with plasma levels ranging from 102 to 108 copies of viral DNA\ml. TTV is a small unenveloped virus with a single-stranded circular DNA genome of negative polarity of approximately 3,8 kB. TTV titres in plasma sample can have broad fluctuations or remain rather stable over protracted periods of time. Although many works have been aimed to explore the pathogenicity of the virus, TTV is still considered an orphan virus, not associated with human diseases. Recently, variations in TTV viremia have been observed being dependent on the immunological status of the host, since its replication ability is related with the immune system activity. To investigate the relationship between TTV and the immune system, in this research project we examined the TTV’s viral load in patients undergoing bone marrow and\or solid organ transplant (liver, kidney\pancreas), and we correlated the pattern of viral titer with some parameters measured in the course of infection: concentration of CD8+57+ T lymphocytes and the intensity of drug therapy administered. Patients were subjected to longitudinal blood samples and presence and loads of TTV were determined by real-time PCR. In bone marrow transplant patients, the percentage of CD8+57+ T lymphocytes was estimeted by immunophenotyping and flow cytometry. The expansion of this lymphocytes subpopulations is known to occurs after bone marrow transplantation and during some chronic infections and is indicative of immune dysfunction. The results obtained demonstrate that an impaired immune system (in our case due to immunosuppressive therapy pre and post transplant) promotes TTV replication and then an increase of TTV titres in transplant patients’s plasma. In bone marrow transplant patients TTV viremia increased post-transplant and correlated with the expansion of CD8+CD57+ T lymphocytes. In solid organ transplant patients, increase of TTV viremia was more intense in those patients who had received drug therapy

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more powerful. In conclusion, we showed that monitoring TTV plasma levels over time might indeed help in determining when the patient’s immune system has recovered a good level of functionality.

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