Epstein-Barr Virus DNAemia Is an Early Surrogate Marker of the Net State of Immunosuppresion in Solid Organ Transplant Recipients

Juan, Rafael San; Dios, Begoña de; Navarro, David; García‐Reyne, Ana; Lumbreras, Carlos; Bravo, Dayana; Costa, Elisa; Morales, José; Andrés, Amado Philip de; Jiménez-Romero, Carlos; Delgado, Juan Marcelo; Fernández‐Ruiz, Mario; López‐Medrano, Francisco; Aguado, José María

doi:10.1097/tp.0b013e31827a4bd6

Cited by 20 publications

(21 citation statements)

References 18 publications

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“…Such information is important because most PTLD in this population presents late, beyond the first year, and over 50% of late cases are associated with EBV infection (8,9). In addition, there are conflicting analyses relating to the associations of EBV DNAemia with PTLD development, graft dysfunction and loss, acute rejection, opportunistic infection, adverse events, risk of death and overall burden of immunosuppression (6,7,12,(14)(15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Morton¹,

Coupes²,

Roberts

et al. 2014

American Journal of Transplantation

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Epstein-Barr virus (EBV) DNAemia in the first year posttransplantation has been studied extensively. There is a paucity of information on prevalence and sequelae of EBV infection in adult renal transplantation beyond the first year. This single-center study examines the relationship between EBV DNAemia and demographic, immunosuppressive, hematologic and infection-related parameters in 499 renal transplant recipients between 1 month and 33 years posttransplant. Participants were tested repeatedly for EBV DNAemia detection over 12 months and clinical progress followed for 3 years. Prevalence of DNAemia at recruitment increased significantly with time from transplant. In multivariate adjusted analyses, variables associated with DNAemia included EBV seronegative status at transplant (p ¼ 0.045), nonWhite ethnicity (p ¼ 0.014) and previous posttransplant lymphoproliferative disease (PTLD) diagnosis (p ¼ 0.006), while low DNAemia rates were associated with mycophenolate mofetil use (p < 0.0001) and EBV viral capsid antigen positive Epstein-Barr nuclear antigen-1 positive serostatus at transplant (p ¼ 0.044). Patient and graft survival, rate of kidney function decline and patient reported symptoms were not significantly different between EBV DNAemia positive and negative groups. EBV DNAemia is common posttransplant and increases with time from transplantation, but EBV DNAemia detection in low-risk (seropositive) patients has poor specificity as a biomarker for future PTLD risk.

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Section: Discussionmentioning

confidence: 99%

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Morton¹,

Coupes²,

Roberts

et al. 2014

American Journal of Transplantation

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“…Cumulative incidence curves were constructed for study outcomes (overall and bacterial infection and CMV diseases) with death treated as a competing risk, and differences between groups were compared with the log-rank test. Uni-and multivariate Cox regression models were used to evaluate the association between iATP categories at each point (baseline and months 1 and 6 after transplantation) and outcomes throughout the following periods (early [first month], intermediate [months [1][2][3][4][5][6], and late periods [months [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24], respectively) [1]. Associations were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).…”

Section: Discussionmentioning

confidence: 99%

“…A detailed description of the 13 cases of CMV disease diagnosed in the intermediate period in which iATP levels at month 1 were available is provided as Supporting Information (Table S2). Finally, there were no significant differences in the incidence of infection at the end of the late period (i.e., months [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] according to the CMI response at month 6.…”

Section: Risk Of Infection Across Different Categories Of CMI Responsementioning

confidence: 99%

“…The application of immune monitoring strategies has been proposed as an approach to minimize the risk of such complication by tailoring immunosuppressive therapy to individual needs [2]. Different biomarkers [3][4][5][6][7] have been used as surrogates for the overall amount of immunosuppression, although most of these strategies are limited by the lack of technical standardization and validated cutoff values [2]. In addition, certain parameters -such as the enumeration of peripheral blood lymphocyte subpopulations (PBLSs) -do not provide functional insight into the recipient's immune response [2].…”

Section: Introductionmentioning

confidence: 99%

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Monitoring of intracellular adenosine triphosphate in CD4⁺T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients

et al. 2016

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SUMMARYThe measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4 + T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; Pvalue = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.

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“…El punto de corte para hablar de carga viral alta no ha sido establecido y varía entre estudios. Algunos autores sugieren 1500 copias/mL 18 , otros permiten hasta 10 000 copias/mL 19 y 16 000 copias/ mL…”

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Seguimiento con carga viral para virus Epstein- Barr en pacientes pediátricos con trasplante hepático

Mesa

Aristizábal

2015

Rev. Medicas UIS

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RESUMENIntroducción: Los pacientes trasplantados son un reto desde todo punto de vista. La infección por el virus de Epstein-Barr es frecuente y su manejo suele ser difícil por la falta de medicamentos efectivos. Los pacientes con trasplante hepático tienen una alta incidencia de infección/reactivación por virus Epstein-Barr por el riesgo de primoinfección durante este periodo o la reactivación por inmunosupresión. Objetivos: Describir los hallazgos obtenidos con el uso de la carga viral para el virus de Epstein-Barr en el seguimiento de los pacientes pediátricos sometidos a trasplante hepático en una institución de cuarto nivel en Medellín, Colombia. Selección de pacientes: Se revisaron siete historias clínicas de pacientes con trasplante hepáticos escogidos al azar, obteniendo de ellas los datos demográficos, motivo de trasplante, momento de la aparición de la de la carga viral positiva por el virus de Epstein-Barr, evolución de la carga viral, efectos de los medicamentos inmunosupresores y antivirales, y el desenlace de los pacientes. Descripción de casos: La edad promedio de los pacientes al momento del trasplante fue de 28,4 meses, el efecto de los medicamentos antivirales como gangiclovir, valganciclovir, inmunoglobulina contra citomegalovirus, no parece ejercer una disminución adecuada y sostenida de la carga viral. Conclusiones: A pesar de las opciones terapéuticas disponibles para el herpes virus, según lo encontrado en la literatura actual y lo visto los pacientes evaluados, el grado de inmunosupresión parece ser el principal factor para el control de la replicación del virus de Epstein-Barr. Follow up with viral load monitoring for Epstein-Barr virus in pediatric pacients with hepatic transplantABSTRACT Introduction: Transplant patients are a challenge from every point of view. Infection with Epstein-Barr virus is common and management is often hampered by the lack of effective medicaments available. Liver transplant patients have a high incidence of Epstein-Barr virus infection / reactivation because of the the risk of primary infection during this period or immunosuppression associated reactivation. Objectives: Describe the findings when using EBV viral load monitoring in liver transplant patients in an institution of the fourth level in Medellin, Colombia. Selection of patients: Seven medical records from liver transplant patients were randomly chosen obtaining from them demographic data, cause of transplantation, time of the Epstein-Barr virus detection, viral load evolution, effects of immunosuppressive medications over them and the patient´s outcome. Description of patients: Average patient age at transplant was 28,4 months, the effect of antiviral drugs (gangiclovir, valganciclovir, cytomegalovirus immunoglobulin) seems not to be adequate and sustained in decreasing viral load. Conclusions: Although the therapeutic options available for Herpes virus , as found in current literature and seen in our patients, immunosupression degree seems to be the main factor for controlling EBV replication. MÉ...

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Epstein-Barr Virus DNAemia Is an Early Surrogate Marker of the Net State of Immunosuppresion in Solid Organ Transplant Recipients

Abstract: Persistent and high levels of EBVd within the first 6 months after SOT are surrogate markers of increased risk of IRAE.

Cited by 20 publications

References 18 publications

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Monitoring of intracellular adenosine triphosphate in CD4⁺T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients

Seguimiento con carga viral para virus Epstein- Barr en pacientes pediátricos con trasplante hepático

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Epstein-Barr Virus DNAemia Is an Early Surrogate Marker of the Net State of Immunosuppresion in Solid Organ Transplant Recipients

Abstract: Persistent and high levels of EBVd within the first 6 months after SOT are surrogate markers of increased risk of IRAE.

Cited by 20 publications

References 18 publications

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Monitoring of intracellular adenosine triphosphate in CD4+T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients

Seguimiento con carga viral para virus Epstein- Barr en pacientes pediátricos con trasplante hepático

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Monitoring of intracellular adenosine triphosphate in CD4⁺T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients