Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation
Polyomavirus BK (BKPyV)-associated nephropathy (BKPyV-nephropathy) remains a significant cause of premature kidney allograft failure. In the absence of effective antiviral treatments, current therapeutic approaches rely on immunosuppression (IS) reduction, possibly at the risk of inducing alloimmuni...
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2024-12-01
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| author | Michela Cioni Stella Muscianisi Marica De Cicco Sabrina Basso Hans H. Hirsch Iris Fontana Laura Catenacci Jessica Bagnarino Mariangela Siciliano Oriana Montana Lampo Gloria Acquafredda Lou Tina Diana Boti Jessica Rotella Eleonora Bozza Jennifer Zumelli Kristiana Mebelli Fausto Baldanti Massimo Cardillo Marco Zecca Arcangelo Nocera Mario Luppi Enrico Verrina Fabrizio Ginevri Patrizia Comoli |
| author_facet | Michela Cioni Stella Muscianisi Marica De Cicco Sabrina Basso Hans H. Hirsch Iris Fontana Laura Catenacci Jessica Bagnarino Mariangela Siciliano Oriana Montana Lampo Gloria Acquafredda Lou Tina Diana Boti Jessica Rotella Eleonora Bozza Jennifer Zumelli Kristiana Mebelli Fausto Baldanti Massimo Cardillo Marco Zecca Arcangelo Nocera Mario Luppi Enrico Verrina Fabrizio Ginevri Patrizia Comoli |
| author_sort | Michela Cioni |
| collection | DOAJ |
| description | Polyomavirus BK (BKPyV)-associated nephropathy (BKPyV-nephropathy) remains a significant cause of premature kidney allograft failure. In the absence of effective antiviral treatments, current therapeutic approaches rely on immunosuppression (IS) reduction, possibly at the risk of inducing alloimmunity. Therefore, we sought to explore the long-term effects of a tailored viro-immunologic surveillance and treatment program for BKPyV on the development of alloimmunity and kidney graft outcome. Forty-five pediatric kidney transplant recipients were longitudinally monitored for BKPyV replication, virus-specific immunity, and donor-specific HLA antibodies (DSAs). DNAemia developed in 15 patients who were treated with stepwise IS reduction. Among the other 30 patients, 17 developed DNAuria without DNAemia and 13 always resulted as BKPyV-negative. All patients with DNAemia cleared BKPyV after having mounted a virus-specific cellular immune response, and no biopsy-proven BKPyV-nephropathy was observed. The presence of cytotoxic populations directed to the BKPyV Large-T (LT) antigen early after transplantation protected kidney recipients from developing BKPyV replication, and the appearance of LT-specific T cells in viruric patients prevented the development of BKPyV-DNAemia. In our cohort, no significant correlation was observed between BKPyV-DNAemia and the development of DSA and antibody-mediated rejection. However, patients who experienced and cleared BKPyV-DNAemia had a worse allograft survival at a median follow-up of 18.9 years (<i>p</i> = 0.048). These data need to be confirmed in larger cohorts. |
| format | Article |
| id | doaj-art-bf19b8f71b3144b29222b2107912f3f8 |
| institution | Kabale University |
| issn | 2076-2607 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj-art-bf19b8f71b3144b29222b2107912f3f82025-01-24T13:42:25ZengMDPI AGMicroorganisms2076-26072024-12-011314810.3390/microorganisms13010048Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney TransplantationMichela Cioni0Stella Muscianisi1Marica De Cicco2Sabrina Basso3Hans H. Hirsch4Iris Fontana5Laura Catenacci6Jessica Bagnarino7Mariangela Siciliano8Oriana Montana Lampo9Gloria Acquafredda10Lou Tina Diana Boti11Jessica Rotella12Eleonora Bozza13Jennifer Zumelli14Kristiana Mebelli15Fausto Baldanti16Massimo Cardillo17Marco Zecca18Arcangelo Nocera19Mario Luppi20Enrico Verrina21Fabrizio Ginevri22Patrizia Comoli23Fondazione Malattie Renali del Bambino, IRCCS G. Gaslini Institute, 16147 Genova, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyTransplantation and Clinical Virology, Department of Biomedicine, University of Basel, 4009 Basel, SwitzerlandVascular and Endovascular Department, Kidney Transplant Surgery Unit, Ospedale Policlinico San Martino, 16132 Genova, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyMicrobiology and Virology, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyMicrobiology and Virology, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyTransplantation Immunology, Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milano, ItalyPediatric Hematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyFondazione Malattie Renali del Bambino, IRCCS G. Gaslini Institute, 16147 Genova, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalyFondazione Malattie Renali del Bambino, IRCCS G. Gaslini Institute, 16147 Genova, ItalyFondazione Malattie Renali del Bambino, IRCCS G. Gaslini Institute, 16147 Genova, ItalyCell Factory, Department of Mother and Child Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyPolyomavirus BK (BKPyV)-associated nephropathy (BKPyV-nephropathy) remains a significant cause of premature kidney allograft failure. In the absence of effective antiviral treatments, current therapeutic approaches rely on immunosuppression (IS) reduction, possibly at the risk of inducing alloimmunity. Therefore, we sought to explore the long-term effects of a tailored viro-immunologic surveillance and treatment program for BKPyV on the development of alloimmunity and kidney graft outcome. Forty-five pediatric kidney transplant recipients were longitudinally monitored for BKPyV replication, virus-specific immunity, and donor-specific HLA antibodies (DSAs). DNAemia developed in 15 patients who were treated with stepwise IS reduction. Among the other 30 patients, 17 developed DNAuria without DNAemia and 13 always resulted as BKPyV-negative. All patients with DNAemia cleared BKPyV after having mounted a virus-specific cellular immune response, and no biopsy-proven BKPyV-nephropathy was observed. The presence of cytotoxic populations directed to the BKPyV Large-T (LT) antigen early after transplantation protected kidney recipients from developing BKPyV replication, and the appearance of LT-specific T cells in viruric patients prevented the development of BKPyV-DNAemia. In our cohort, no significant correlation was observed between BKPyV-DNAemia and the development of DSA and antibody-mediated rejection. However, patients who experienced and cleared BKPyV-DNAemia had a worse allograft survival at a median follow-up of 18.9 years (<i>p</i> = 0.048). These data need to be confirmed in larger cohorts.https://www.mdpi.com/2076-2607/13/1/48pediatric kidney transplantationpolyomavirus BKcellular immunityhumoral immunitydonor-specific antibodies |
| spellingShingle | Michela Cioni Stella Muscianisi Marica De Cicco Sabrina Basso Hans H. Hirsch Iris Fontana Laura Catenacci Jessica Bagnarino Mariangela Siciliano Oriana Montana Lampo Gloria Acquafredda Lou Tina Diana Boti Jessica Rotella Eleonora Bozza Jennifer Zumelli Kristiana Mebelli Fausto Baldanti Massimo Cardillo Marco Zecca Arcangelo Nocera Mario Luppi Enrico Verrina Fabrizio Ginevri Patrizia Comoli Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation Microorganisms pediatric kidney transplantation polyomavirus BK cellular immunity humoral immunity donor-specific antibodies |
| title | Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation |
| title_full | Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation |
| title_fullStr | Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation |
| title_full_unstemmed | Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation |
| title_short | Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation |
| title_sort | control of bkpyv dnaemia by a tailored viro immunologic approach does not lead to bkpyv nephropathy progression and development of donor specific antibodies in pediatric kidney transplantation |
| topic | pediatric kidney transplantation polyomavirus BK cellular immunity humoral immunity donor-specific antibodies |
| url | https://www.mdpi.com/2076-2607/13/1/48 |
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