Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study

Torque teno virus (TTV) was recently identified as a potential biomarker for the degree of immunosuppression, and potentially as a predictor of rejection and infection in solid organ transplant patients. We evaluated TTV viral load in kidney transplant (KT) patients during the first year post-transp...

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Main Authors: Sara Querido, Catarina Martins, Perpétua Gomes, Maria Ana Pessanha, Maria Jorge Arroz, Teresa Adragão, Ana Casqueiro, Regina Oliveira, Inês Costa, Jorge Azinheira, Paulo Paixão, André Weigert
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Language:English
Published: MDPI AG 2023-06-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/15/7/1464
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author Sara Querido
Catarina Martins
Perpétua Gomes
Maria Ana Pessanha
Maria Jorge Arroz
Teresa Adragão
Ana Casqueiro
Regina Oliveira
Inês Costa
Jorge Azinheira
Paulo Paixão
André Weigert
author_facet Sara Querido
Catarina Martins
Perpétua Gomes
Maria Ana Pessanha
Maria Jorge Arroz
Teresa Adragão
Ana Casqueiro
Regina Oliveira
Inês Costa
Jorge Azinheira
Paulo Paixão
André Weigert
author_sort Sara Querido
collection DOAJ
description Torque teno virus (TTV) was recently identified as a potential biomarker for the degree of immunosuppression, and potentially as a predictor of rejection and infection in solid organ transplant patients. We evaluated TTV viral load in kidney transplant (KT) patients during the first year post-transplant to examine overall kinetics and their relationships with deleterious events, including episodes of infection and the formation of de novo donor-specific antibodies (DSAs). In a single-center, prospective observational cohort study, 81 KT patients were monitored at baseline, week 1, and month 1, 3, 6, 9 and 12, post-KT, and whenever required by clinical events. Kidney function, plasma TTV load, immunoglobulins and lymphocyte subpopulations were assessed at each time point. Twenty-six patients (32.1%) presented a total of 38 infection episodes post-KT. Induction immunosuppression with thymoglobulin, compared to basiliximab, was not associated with more infections (<i>p</i> = 0.8093). Patients with infectious events had lower T-cells (<i>p</i> = 0.0500), CD8<sup>+</sup> T-cells (<i>p</i> = 0.0313) and B-cells (<i>p</i> = 0.0009) 1 month post-KT, compared to infection-free patients. Patients with infection also showed higher increases in TTV viral loads between week 1- month 1, post-KT, with TTV viral load variations >2.65 log<sub>10</sub> cp/mL predicting the development of infectious events during the 12-month study period (<i>p</i> < 0.0001; sensitivity 99.73%; specificity 83.67%). Patients who developed de novo DSAs had lower TTV DNA viral loads at month 12 after KT, compared to patients who did not develop DSA (3.7 vs. 5.3 log<sub>10</sub> cp/mL, <i>p</i> = 0.0023). Briefly, evaluating early TTV viremia is a promising strategy for defining infectious risk in the 1st year post-KT. The availability of standardized commercial real-time PCR assays is crucial to further validate this as an effective tool guiding immunosuppression prescription.
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spelling doaj.art-7a6e78ae2ce04c1483b80dae04fc7a602023-11-18T21:44:04ZengMDPI AGViruses1999-49152023-06-01157146410.3390/v15071464Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort StudySara Querido0Catarina Martins1Perpétua Gomes2Maria Ana Pessanha3Maria Jorge Arroz4Teresa Adragão5Ana Casqueiro6Regina Oliveira7Inês Costa8Jorge Azinheira9Paulo Paixão10André Weigert11Renal Transplantation Unit, Nephrology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, 2790-134 Carnaxide, PortugalImmune Dysregulation from Pregnancy to Adulthood Research Group, CHRC—Comprehensive Health Research Center, NOVA Medical School, Faculdade de Ciências Médicas (NMS|FCM), Universidade NOVA de Lisboa, 1150-082 Lisboa, PortugalLaboratory of Clinical Microbiology and Molecular Biology, Department of Clinical Pathology, Centro Hospitalar de Lisboa Ocidental, 1349-019 Lisboa, PortugalLaboratory of Clinical Microbiology and Molecular Biology, Department of Clinical Pathology, Centro Hospitalar de Lisboa Ocidental, 1349-019 Lisboa, PortugalFlow Cytometry Laboratory, Department of Clinical Pathology, Centro Hospitalar de Lisboa Ocidental, 1349-019 Lisboa, PortugalRenal Transplantation Unit, Nephrology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, 2790-134 Carnaxide, PortugalRenal Transplantation Unit, Nephrology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, 2790-134 Carnaxide, PortugalRenal Transplantation Unit, Nephrology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, 2790-134 Carnaxide, PortugalLaboratory of Clinical Microbiology and Molecular Biology, Department of Clinical Pathology, Centro Hospitalar de Lisboa Ocidental, 1349-019 Lisboa, PortugalLaboratory of Biochemistry, Department of Clinical Pathology, Centro Hospitalar de Lisboa Ocidental, 1349-019 Lisboa, PortugalInfection, Sepsis & Antibiotics Resistance Research Group, CHRC—Comprehensive Health Research Center, NOVA Medical School, Faculdade de Ciências Médicas (NMS|FCM), Universidade NOVA de Lisboa, 1150-082 Lisboa, PortugalRenal Transplantation Unit, Nephrology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, 2790-134 Carnaxide, PortugalTorque teno virus (TTV) was recently identified as a potential biomarker for the degree of immunosuppression, and potentially as a predictor of rejection and infection in solid organ transplant patients. We evaluated TTV viral load in kidney transplant (KT) patients during the first year post-transplant to examine overall kinetics and their relationships with deleterious events, including episodes of infection and the formation of de novo donor-specific antibodies (DSAs). In a single-center, prospective observational cohort study, 81 KT patients were monitored at baseline, week 1, and month 1, 3, 6, 9 and 12, post-KT, and whenever required by clinical events. Kidney function, plasma TTV load, immunoglobulins and lymphocyte subpopulations were assessed at each time point. Twenty-six patients (32.1%) presented a total of 38 infection episodes post-KT. Induction immunosuppression with thymoglobulin, compared to basiliximab, was not associated with more infections (<i>p</i> = 0.8093). Patients with infectious events had lower T-cells (<i>p</i> = 0.0500), CD8<sup>+</sup> T-cells (<i>p</i> = 0.0313) and B-cells (<i>p</i> = 0.0009) 1 month post-KT, compared to infection-free patients. Patients with infection also showed higher increases in TTV viral loads between week 1- month 1, post-KT, with TTV viral load variations >2.65 log<sub>10</sub> cp/mL predicting the development of infectious events during the 12-month study period (<i>p</i> < 0.0001; sensitivity 99.73%; specificity 83.67%). Patients who developed de novo DSAs had lower TTV DNA viral loads at month 12 after KT, compared to patients who did not develop DSA (3.7 vs. 5.3 log<sub>10</sub> cp/mL, <i>p</i> = 0.0023). Briefly, evaluating early TTV viremia is a promising strategy for defining infectious risk in the 1st year post-KT. The availability of standardized commercial real-time PCR assays is crucial to further validate this as an effective tool guiding immunosuppression prescription.https://www.mdpi.com/1999-4915/15/7/1464Torquetenovirusimmunosuppressionkidney transplantinfectiondonor-specific antibodies
spellingShingle Sara Querido
Catarina Martins
Perpétua Gomes
Maria Ana Pessanha
Maria Jorge Arroz
Teresa Adragão
Ana Casqueiro
Regina Oliveira
Inês Costa
Jorge Azinheira
Paulo Paixão
André Weigert
Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study
Viruses
Torquetenovirus
immunosuppression
kidney transplant
infection
donor-specific antibodies
title Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study
title_full Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study
title_fullStr Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study
title_full_unstemmed Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study
title_short Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study
title_sort kinetics of torque teno virus viral load is associated with infection and de novo donor specific antibodies in the first year after kidney transplantation a prospective cohort study
topic Torquetenovirus
immunosuppression
kidney transplant
infection
donor-specific antibodies
url https://www.mdpi.com/1999-4915/15/7/1464
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