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Erik A M Verschuuren - One of the best experts on this subject based on the ideXlab platform.
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Plenary paper Frequent
2016Co-Authors: Servi J C Stevens, Chris J L M Meijer, Erik A M Verschuuren, Wim Van Der Bij, Inge Pronk, Martin C Harmsen, Hauw T. The, Jaap M MiddeldorpAbstract:monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of Posttransplant Lymphoproliferative Disease in high-risk patient
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epstein barr virus dna load monitoring late after lung transplantation a surrogate marker of the degree of immunosuppression and a safe guide to reduce immunosuppression
Transplantation, 2007Co-Authors: Nicolaas A Bakker, Erik A M Verschuuren, Nic J G M Veeger, Bouke G Hepkema, Michiel E Erasmus, Cees G M KallenbergAbstract:Background. Posttransplant Lymphoproliferative Disease (PTLD) is a serious complication after lung transplantation and its relation with Epstein-Barr virus (EBV) is well recognized. It has been postulated that preemptive reduction of immunosuppression guided by EBV-DNA load may lead to a significantly lower incidence of PTLD, because of the reconstitution of T-cell control. In this report, we describe the feasibility of this approach in terms of safety with regard to the risk of acute as well as chronic allograft rejection in 75 lung transplant recipients transplanted between 1990 and 2001 and followed for this study from June 1, 2001 until January 1, 2006. Methods. From all patients visiting our outpatient clinic, EBV-DNA load was measured at least twice a year during the study period. In patients with positive results, measurements were repeated every two to four weeks. EBV reactivation was defined as two consecutive EBV-DNA load measurements with a rising trend; with the last measurement exceeding 10.000 copies/mL under stable immunosuppression. In such case, immunosuppression was reduced. Results. EBV reactivation was observed in 26/75 patients (35%). One (1.5%) of these patients developed PTLD during the study period. Acute rejection, acceleration of chronic allograft rejection, or worse survival were not observed after reduction of immunosuppression. Conclusions. Preemptive reduction of immunosuppression after lung transplantation guided by EBV-DNA load appears to be a safe approach for the prevention of PTLD in lung transplant recipients late after transplantation.
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hla antigens and post renal transplant Lymphoproliferative Disease hla b matching is critical
Transplantation, 2005Co-Authors: Nicolaas A Bakker, Gustaaf W Van Imhoff, Erik A M Verschuuren, Willem J Van Son, Jaap Homan J Van Der Heide, Simon P M Lems, Nic J G M Veeger, Philip M Kluin, Hanneke C Kluinnelemans, Bouke G HepkemaAbstract:Although several risk factors for Posttransplant Lymphoproliferative Disease (PTLD) after solid organ transplantation have been identified, the immunosuppressive regimen probably as most important one, their exact pathogenic role and relevance is still unclear. In hematopoietic stem cell transplantation, HLA mismatching also is a risk factor. We analyzed factors possibly associated with development of PTLD in patients receiving a kidney transplant at our hospital between 1985 and 2002. PTLD was observed in 20 out of 1,013 patients (2.0%). Mismatches at the HLA-B locus, but not at the HLA-A or HLA-DR loci, and anti T-cell antibody therapy were both independently associated with development of PTLD. Hazard ratios increased from 1.4 (0.5-4.1) with one mismatch to 5.1 (1.4-19.0) in case of two HLA-B mismatches. Decreased surveillance by T-cells with dual specificity for Epstein-Barr virus (EBV) as well as for allo HLA antigens on the allograft might facilitate clonal expansion of B-cells latently infected with EBV.
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treatment of Posttransplant Lymphoproliferative Disease with rituximab the remission the relapse and the complication
Transplantation, 2002Co-Authors: Erik A M Verschuuren, Gustaaf W Van Imhoff, Servi J C Stevens, Jaap M Middeldorp, Conny De Boer, Gerard H Koeter, Wim Van Der BijAbstract:Background. Rituximab, a humanized anti-CD20 monoclonal antibody, is a promising new tool for the treatment of Posttransplant Lymphoproliferative Disease (PTLD), especially for patients transplanted with rejection prone transplants of vital organs, such as patients after lung transplantation. Thus far, no major complications have been described. We treated three lung transplant recipients with Rituximab because of PTLD. Methods. Patients were treated with four weekly doses of 375 mg/m(2) of Rituximab. Epstein-Barr virus (EBV) DNA was monitored with quantitative-competitive polymerase chain reaction and circulating B cells with flow cytometry. Results. Treatment with Rituximab resulted in a complete remission in all patients without signs of or progression of bronchiolitis obliterans syndrome. Patient 1 relapsed after 2 months with a partly CD20-negative PTLD but is in stable remission after radiotherapy. Patient 2 is in complete remission 16 months after treatment, but patient 3 developed a hypogammaglobulinemia and died of invasive aspergillosis after 6 months. EBV DNA was detectable in the blood samples of patients 2 and 3 before treatment with Rituximab and became negative instantly after Rituximab. In all three patients, B cells am absent in the peripheral blood 7 months (at death), 16 months, and 16 months after treatment with Rituximab. Antiproliferating agents, such as mycophenolate mofetil (MMF), might prolong B-cell depletion. Conclusions. Rituximab was effective for the treatment of PTLD without progression of transplant dysfunction in our patients. Complications were a partly CD20-negative relapse of PTLD and a hypogammaglobulinemia. Attention should be paid to immunoglobulin G (IgG) levels, especially in patients treated with antiproliferating agents such as MMF.
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frequent monitoring of epstein barr virus dna load in unfractionated whole blood is essential for early detection of Posttransplant Lymphoproliferative Disease in high risk patients
Blood, 2001Co-Authors: Servi J C Stevens, Chris J L M Meijer, Erik A M Verschuuren, Wim Van Der Bij, Inge Pronk, Martin C Harmsen, Adriaan J C Van Den Brule, Jaap M MiddeldorpAbstract:Posttransplant Lymphoproliferative Disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)–associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative competitive polymerase chain reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the majority of patients having high viral loads before and at PTLD diagnosis. Especially in a primary EBV-infected patient and in patients with conversion of immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4% of the whole blood samples was above the cut-off value (P
Jaap M Middeldorp - One of the best experts on this subject based on the ideXlab platform.
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sequence variation of epstein barr virus viral types geography codon usage and Diseases
Journal of Virology, 2018Co-Authors: Samantha Correia, Jaap M Middeldorp, Ray Bridges, Fanny Wegner, Cristina Venturini, Anne L Palser, Jeffrey I Cohen, Mario Alejandro Lorenzetti, Irene Bassano, Robert E WhiteAbstract:One hundred thirty-eight new Epstein-Barr virus (EBV) genome sequences have been determined. One hundred twenty-five of these and 116 from previous reports were combined to produce a multiple-sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type 2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 single-nucleotide polymorphisms (SNPs) at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART microRNA region of the genome was present in 21 EBV strains. EBV from saliva of U.S. patients with chronic active EBV infection aligned with the wild-type EBV genome with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases from both Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes, and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and Posttransplant Lymphoproliferative Disease. It contributes to several types of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. EBV genome variation is important because some of the Diseases associated with EBV have very different incidences in different populations and geographic regions, and differences in the EBV genome might contribute to these Diseases. Some specific EBV genome alterations that appear to be significant in EBV-associated cancers are already known, and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets.
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Plenary paper Frequent
2016Co-Authors: Servi J C Stevens, Chris J L M Meijer, Erik A M Verschuuren, Wim Van Der Bij, Inge Pronk, Martin C Harmsen, Hauw T. The, Jaap M MiddeldorpAbstract:monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of Posttransplant Lymphoproliferative Disease in high-risk patient
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treatment of Posttransplant Lymphoproliferative Disease with rituximab the remission the relapse and the complication
Transplantation, 2002Co-Authors: Erik A M Verschuuren, Gustaaf W Van Imhoff, Servi J C Stevens, Jaap M Middeldorp, Conny De Boer, Gerard H Koeter, Wim Van Der BijAbstract:Background. Rituximab, a humanized anti-CD20 monoclonal antibody, is a promising new tool for the treatment of Posttransplant Lymphoproliferative Disease (PTLD), especially for patients transplanted with rejection prone transplants of vital organs, such as patients after lung transplantation. Thus far, no major complications have been described. We treated three lung transplant recipients with Rituximab because of PTLD. Methods. Patients were treated with four weekly doses of 375 mg/m(2) of Rituximab. Epstein-Barr virus (EBV) DNA was monitored with quantitative-competitive polymerase chain reaction and circulating B cells with flow cytometry. Results. Treatment with Rituximab resulted in a complete remission in all patients without signs of or progression of bronchiolitis obliterans syndrome. Patient 1 relapsed after 2 months with a partly CD20-negative PTLD but is in stable remission after radiotherapy. Patient 2 is in complete remission 16 months after treatment, but patient 3 developed a hypogammaglobulinemia and died of invasive aspergillosis after 6 months. EBV DNA was detectable in the blood samples of patients 2 and 3 before treatment with Rituximab and became negative instantly after Rituximab. In all three patients, B cells am absent in the peripheral blood 7 months (at death), 16 months, and 16 months after treatment with Rituximab. Antiproliferating agents, such as mycophenolate mofetil (MMF), might prolong B-cell depletion. Conclusions. Rituximab was effective for the treatment of PTLD without progression of transplant dysfunction in our patients. Complications were a partly CD20-negative relapse of PTLD and a hypogammaglobulinemia. Attention should be paid to immunoglobulin G (IgG) levels, especially in patients treated with antiproliferating agents such as MMF.
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frequent monitoring of epstein barr virus dna load in unfractionated whole blood is essential for early detection of Posttransplant Lymphoproliferative Disease in high risk patients
Blood, 2001Co-Authors: Servi J C Stevens, Chris J L M Meijer, Erik A M Verschuuren, Wim Van Der Bij, Inge Pronk, Martin C Harmsen, Adriaan J C Van Den Brule, Jaap M MiddeldorpAbstract:Posttransplant Lymphoproliferative Disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)–associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative competitive polymerase chain reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the majority of patients having high viral loads before and at PTLD diagnosis. Especially in a primary EBV-infected patient and in patients with conversion of immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4% of the whole blood samples was above the cut-off value (P
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frequent monitoring of epstein barr virus dna load in unfractionated whole blood is essential for early detection of Posttransplant Lymphoproliferative Disease in high risk patients
Blood, 2001Co-Authors: Servi J C Stevens, Chris J L M Meijer, Erik A M Verschuuren, Inge Pronk, Martin C Harmsen, Adriaan J C Van Den Brule, Jaap M MiddeldorpAbstract:Posttransplant Lymphoproliferative Disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)‐associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative competitive polymerase chain reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the majority of patients having high viral loads before and at PTLD diagnosis. Especially in a primary EBV-infected patient and in patients with conversion of immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4% of the whole blood samples was above the cutoff value (P < .0001) despite heavy immune suppression and cytomegalovirus (CMV)-related Disease. These findings illustrate the clinical importance of frequent EBV DNA load monitoring in LTx recipients. The increased EBV DNA loads in PTLD patients were restricted to the cellular blood compartment, as parallel serum samples were all below cut-off value, which indicates absence of lytic viral replication. EBV 1 cells in PTLD patients have a very short doubling time, which can be as low as 56 hours, thereby creating the need for high screening frequency in high-risk patients. Furthermore, it is shown that EBV and CMV can reactivate independently in LTx recipients and that EBV DNA load monitoring may be useful in discriminating PTLD from rejection. (Blood. 2001;97:1165-1171)
Robert E White - One of the best experts on this subject based on the ideXlab platform.
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sequence variation of epstein barr virus viral types geography codon usage and Diseases
Journal of Virology, 2018Co-Authors: Samantha Correia, Jaap M Middeldorp, Ray Bridges, Fanny Wegner, Cristina Venturini, Anne L Palser, Jeffrey I Cohen, Mario Alejandro Lorenzetti, Irene Bassano, Robert E WhiteAbstract:One hundred thirty-eight new Epstein-Barr virus (EBV) genome sequences have been determined. One hundred twenty-five of these and 116 from previous reports were combined to produce a multiple-sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type 2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 single-nucleotide polymorphisms (SNPs) at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART microRNA region of the genome was present in 21 EBV strains. EBV from saliva of U.S. patients with chronic active EBV infection aligned with the wild-type EBV genome with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases from both Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes, and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and Posttransplant Lymphoproliferative Disease. It contributes to several types of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. EBV genome variation is important because some of the Diseases associated with EBV have very different incidences in different populations and geographic regions, and differences in the EBV genome might contribute to these Diseases. Some specific EBV genome alterations that appear to be significant in EBV-associated cancers are already known, and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets.
Steve E Woodle - One of the best experts on this subject based on the ideXlab platform.
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epstein barr virus induced Posttransplant Lymphoproliferative disorders
Transplantation, 1999Co-Authors: Carlos V Paya, Elliott Kieff, Michael A Nalesnik, John J Fung, Michael R Green, Gregory J Gores, Thomas M Habermann, Russell H Wiesner, Lode J Swinnen, Steve E WoodleAbstract:Epstein-Barr virus-induced Posttransplant Lymphoproliferative Disease (EBV-PTLD) continues to be a major complication after solid organ transplantation in high-risk patients. Despite the identification of risk factors that predispose patients to develop EBV-PTLD, limitations in our knowledge of its pathogenesis, variable criteria for establishing the diagnosis, and lack of randomized studies addressing the prevention and treatment of EBV-PTLD hamper the optimal management of this transplant complication. This review summarizes the current knowledge of EBV-PTLD and, as a result of two separate international meetings on this topic, and provides recommendations for future areas of study.
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Posttransplant Lymphoproliferative Disease in pediatric liver transplantation interplay between primary epstein barr virus infection and immunosuppression
Transplantation, 1996Co-Authors: K A Newell, Steve E Woodle, Estella M Alonso, Peter F Whitington, D S Bruce, Michael J Millis, J B Piper, Susan Kelly, Hartmut Koeppen, John HartAbstract:The incidence, risk factors, and outcome of Posttransplant Lymphoproliferative Disease (PTLD) were examined for 298 children undergoing liver transplantation. The overall incidence of PTLD was 8.4% (25 of 298). Intensity of immunosuppression was found to be a major risk factor for the development of PTLD. Cyclosporine and tacrolimus when used as primary immunosuppression were associated with the development of PTLD in 4.3% and 6.6% of cases (P=NS). OKT3 and tacrolimus, when used as rescue therapy for steroid-resistant rejection, were associated with a comparable increase in the risk of developing PTLD (10.9% and 11.1%, P=NS). Patients requiring both OKT3 and tacrolimus to treat refractory rejection were at significantly increased risk for PTLD (28.1% vs. 4.3% or 6.6%, P<0.0001). PTLD was more common in patients who received transplants for Langerhans cell histiocytosis relative to other indications for transplantation (66% vs. 8.4%, P=0.0005). The data also support an association between primary Epstein-Barr virus (EBV) infections following transplantation and the development of PTLD. While only three patients were EBV seropositive before transplantation (14%), 19 patients were EBV seropositive at the time of diagnosis of PTLD (90%), confirming a high incidence of primary EBV infections in patients with PTLD (21 patients had both pre- and Posttransplant EBV serologies). In this series, PTLD was associated with a mortality rate of 60%, and 12 of the 15 patients who died had persistent tumor at the time of death. Five of the 13 patients rendered Disease-free developed ductopenic rejection. Of the four with severe liver dysfunction, two have undergone successful retransplantation and are alive without evidence of PTLD. In conclusion, intense immunosuppression using OKT3 and tacrolimus as rescue agents was associated with a significant increase in the incidence of PTLD. Primary EBV infection after transplantation further accentuated this risk. Independent of these risk factors, patients with Langerhans cell histiocytosis were at significantly increased risk for PTLD. The identification of high-risk patients should allow the development of protocols to screen patients for primary EBV infections and early indications of PTLD, as well as the institution of preemptive antiviral and antitumor therapies.
Samantha Correia - One of the best experts on this subject based on the ideXlab platform.
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sequence variation of epstein barr virus viral types geography codon usage and Diseases
Journal of Virology, 2018Co-Authors: Samantha Correia, Jaap M Middeldorp, Ray Bridges, Fanny Wegner, Cristina Venturini, Anne L Palser, Jeffrey I Cohen, Mario Alejandro Lorenzetti, Irene Bassano, Robert E WhiteAbstract:One hundred thirty-eight new Epstein-Barr virus (EBV) genome sequences have been determined. One hundred twenty-five of these and 116 from previous reports were combined to produce a multiple-sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type 2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 single-nucleotide polymorphisms (SNPs) at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART microRNA region of the genome was present in 21 EBV strains. EBV from saliva of U.S. patients with chronic active EBV infection aligned with the wild-type EBV genome with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases from both Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes, and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and Posttransplant Lymphoproliferative Disease. It contributes to several types of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. EBV genome variation is important because some of the Diseases associated with EBV have very different incidences in different populations and geographic regions, and differences in the EBV genome might contribute to these Diseases. Some specific EBV genome alterations that appear to be significant in EBV-associated cancers are already known, and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets.