AIM To examine the risk of late-onset post-transplant lymphoproliferative disorder(PTLD) in the presence of persisting high Epstein-Barr virus(EBV) in EBV na?ve pediatric heart transplant(HT) recipients. METHODS A ret...AIM To examine the risk of late-onset post-transplant lymphoproliferative disorder(PTLD) in the presence of persisting high Epstein-Barr virus(EBV) in EBV na?ve pediatric heart transplant(HT) recipients. METHODS A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. RESULTS PTLD was diagnosed in 8 out of 145 patients(5.5%); 6/91(6.5%) in those who were EBV seropositive and 2/54(3.7%) in the EBV na?ve group at the time of HT(P = 0.71). We found 32/145(22%) patients with persistently high EBV load during continuing follow-up; 20/91(22%) in EBV seropositive group vs 12/54(22%) in EBV na?ve group(P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant(P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15%(3/20) of patients with high EBV vs 4.2%(3/71) of patients with low or undetectable EBV load(P = 0.14) whereas in EBV na?ve patients 8.3%(1/12) of those withhigh EBV load and 2.3%(1/42) with low or undetectable EBV load(P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up(4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort(P = 0.005). At least one episode of acute rejection occurred in 72%(23/32) of patients with high EBV vs 36%(41/113) patients with low or undetectable EBV after HT(P < 0.05). CONCLUSION There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in immunosuppression.展开更多
Objective:To investigate the effects of hepatitis B virus(HBV)X protein(HBx)on the expression of tumor necrosis factor-α(TNF-α)in glomerular mesangial cells(GMCs)and the underlying intracellular signal pathways.Meth...Objective:To investigate the effects of hepatitis B virus(HBV)X protein(HBx)on the expression of tumor necrosis factor-α(TNF-α)in glomerular mesangial cells(GMCs)and the underlying intracellular signal pathways.Methods:The plasmid pCI-neo-X that carries the X gene of hepatitis B virus was transfected into cultured GMCs.HBx expression in the transfected GMCs was assessed by Western-blot.TNF-αprotein and mRNA were assessed by ELISA and semi-quantitative RT-PCR,respectively.Three kinase inhibitors-U0126,an inhibitor of extracellular signal-regulated kinases(ERKs);lactacvstin,an inhibitor of nuclear factor-κB(NF-κB);and SB203580,a selective inhibitor of p38 MAP kinase(p38 MAPK)were used to determine which intracellular signal pathways may underlie the action of HBx on TNF-αexpression in transfected GMCs.Results:A significant increase in HBx expression in pCI-neo-X transfected GMCs was detected at 36 h and 48 h,which was not affected by any of those kinase inhibitors mentioned above.A similar increase in the expression of both TNF-αprotein and mRNA was also observed at 36 h and 48 h,which was significantly decreased in the presence of U0126 or lactacytin,but not SB203580.Conclusions:HBx upregulates TNF-αexpression in cultured GMCs,possibly through ERKs and NF-κB pathway,but not p38 MAPK pathway.展开更多
文摘AIM To examine the risk of late-onset post-transplant lymphoproliferative disorder(PTLD) in the presence of persisting high Epstein-Barr virus(EBV) in EBV na?ve pediatric heart transplant(HT) recipients. METHODS A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. RESULTS PTLD was diagnosed in 8 out of 145 patients(5.5%); 6/91(6.5%) in those who were EBV seropositive and 2/54(3.7%) in the EBV na?ve group at the time of HT(P = 0.71). We found 32/145(22%) patients with persistently high EBV load during continuing follow-up; 20/91(22%) in EBV seropositive group vs 12/54(22%) in EBV na?ve group(P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant(P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15%(3/20) of patients with high EBV vs 4.2%(3/71) of patients with low or undetectable EBV load(P = 0.14) whereas in EBV na?ve patients 8.3%(1/12) of those withhigh EBV load and 2.3%(1/42) with low or undetectable EBV load(P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up(4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort(P = 0.005). At least one episode of acute rejection occurred in 72%(23/32) of patients with high EBV vs 36%(41/113) patients with low or undetectable EBV after HT(P < 0.05). CONCLUSION There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in immunosuppression.
基金Supported by National Nature Science Foundation of China(GrantNo.30772360)Nature Science Foundation of Health Department of Hubei Province,China(No.JX4B48)Fund of Yangtze University for Doctor(No.2009001)
文摘Objective:To investigate the effects of hepatitis B virus(HBV)X protein(HBx)on the expression of tumor necrosis factor-α(TNF-α)in glomerular mesangial cells(GMCs)and the underlying intracellular signal pathways.Methods:The plasmid pCI-neo-X that carries the X gene of hepatitis B virus was transfected into cultured GMCs.HBx expression in the transfected GMCs was assessed by Western-blot.TNF-αprotein and mRNA were assessed by ELISA and semi-quantitative RT-PCR,respectively.Three kinase inhibitors-U0126,an inhibitor of extracellular signal-regulated kinases(ERKs);lactacvstin,an inhibitor of nuclear factor-κB(NF-κB);and SB203580,a selective inhibitor of p38 MAP kinase(p38 MAPK)were used to determine which intracellular signal pathways may underlie the action of HBx on TNF-αexpression in transfected GMCs.Results:A significant increase in HBx expression in pCI-neo-X transfected GMCs was detected at 36 h and 48 h,which was not affected by any of those kinase inhibitors mentioned above.A similar increase in the expression of both TNF-αprotein and mRNA was also observed at 36 h and 48 h,which was significantly decreased in the presence of U0126 or lactacytin,but not SB203580.Conclusions:HBx upregulates TNF-αexpression in cultured GMCs,possibly through ERKs and NF-κB pathway,but not p38 MAPK pathway.
