Epstein-Barr virus reactivation in renal transplant recipients

Renal transplant recipients at Tygerberg Hospital were investigated to determine the importance of Epstein-Barr virus (EBV) as a pathogen in these patients. All 106 patients investigated were shown to have EBV antibodies before transplantation and most had serological evidence of reactivation of the infection after transplantation. A mild clinical illness was present in a few patients concomitant with EBV reactivation, which may suggest that this virus has a role in the morbidity of some renal transplant recipients. Lymphoblastoid cell lines were established from 11 renal transplant recipients; 5 of these cell lines were shown to be virus producers and 1 is thought to have unique properties.     

Epstein-Barr virus monitoring in paediatric renal transplant recipients

Prospective Epstein-Barr virus (EBV) surveillance post transplant was undertaken by qualitative polymerase chain reaction testing for EBV DNA in plasma so as to detect EBV viremia as early as possible and thereby attempt to pre-empt post-transplant lymphoproliferative disease by reduction of immunosuppression. Forty-three children (46 transplants) were followed for a median (range) of 15.5 (3-25) months. Thirty-one children (67%) were EBV seropositive pre transplant. Twenty children (44%) developed EBV viremia; of these 9 (60%) were seronegative and 11 (36%) seropositive recipients. Primary infection developed later (median difference 14.2 weeks, P=0.009), was more likely to be symptomatic (odds ratio 2.91, 95% confidence interval 0.95-4.88) and associated with a rise in serum creatinine (odds ratio 6.13, 95% confidence interval 4.13-8.13) than reactivation disease. There was a higher incidence of EBV disease in children receiving quadruple therapy and tacrolimus (odds ratio 13.2, 95% confidence interval 11.5-14.9) compared with those given cyclosporin-based immunosuppression. Immunosuppression was reduced when EBV infection was detected. All children became asymptomatic and renal function returned to normal by a median (range) of 17 (6-52) days, although mild relapses occurred in 3 children. Regular EBV surveillance allowed prompt reduction of immunosuppression and was associated with a good outcome in this group of children.     

Epstein-Barr virus antibody responses and clinical illness in renal transplant recipients.

Among 88 renal transplant recipients evaluated for a change in Epstein-Barr virus (EBV) antibody status in the period after transplant, 22 showed a 4-fold rise and eight showed an 8-fold or greater rise in EBV antibody. Among the patients with an 8-fold or greater EBV ANTIBODY RISE, THE OCCURRENCE OF FEVER WAS FREQUENT, ONE PATIENT DEVELOPED A LYMPHOPROLIFERATIVE reaction, and one died with a malignant EBV infection. Patients without pretransplant antibody showed a longer mean time to antibody rise (104 +/- 23 days) than did those patients with pretransplant antibody (19 +/- 7 days). The longer incubation period in patients without pretransplant antibody was in the expected range for primary EBV infections. Both primary and secondary (reactivation) EBV infections occur in renal transplant patients. These infections may be assoicated with prolonged fever, and in unusual circumstances, may cause dramatic lymphoproliferative disease.     

Quantitation of Epstein-Barr virus DNA in the blood of adult liver transplant recipients

BACKGROUND: Posttransplant lymphoproliferation is most often observed in pediatric transplant recipients who experience primary Epstein-Barr virus (EBV) infection at the time of or after transplantation. Lymphoproliferation is believed to be caused by impaired control of EBV-infected cells, which may be of recipient or donor origin. Most studies of EBV infection and lymphoproliferation have focused on the pediatric age group. METHODS: We have undertaken a prospective study of EBV infection in adult liver transplant recipients. Sequentially collected peripheral blood lymphocytes were examined with a recently developed quantitative polymerase chain reaction assay. The assay quantitates EBV DNA genomic titre over a 5 log10 range. RESULTS: Compared with healthy EBV seropositive people not undergoing immunosuppressive therapy, blood EBV DNA titre is elevated in patients with liver disease before transplantation. Overall, highest titres were observed during the first posttransplant month, and in the context of antilymphocyte therapy. In one patient, lymphoproliferation was associated with high titres which fell during reduction of immunosuppressive therapy. In another patient with lymphoproliferation of donor lymphocyte origin, blood EBV DNA titre was not as high. CONCLUSIONS: EBV proliferation is seen in the context of advanced liver disease and after liver transplantation. EBV DNA quantitation is a useful tool to examine the effects of immunosuppression on EBV-associated lymphoproliferation, and may be an essential technique for programs exploring the merits of EBV adoptive immunotherapy.     

BK virus nephropathy in renal transplant recipients

BK virus nephropathy (BKVN) occurs in up to 10% of renal transplant recipients and can result in graft loss. The reactivation of BK virus in renal transplant recipients is largely asymptomatic, and routine surveillance especially in the first 12–24 months after transplant is necessary for early recognition and intervention. Reduced immunosuppression and anti‐viral treatment in the early stages may be effective in stopping BK virus replication. Urinary decoy cells, although highly specific, lack sensitivity to diagnose BKVN. Transplant biopsy remains the gold standard to diagnose BKVN, good surrogate markers for surveillance using quantitative urinary decoy cells, urinary SV40 T immunochemical staining or polyoma virus‐Haufen bodies are offered by recent studies. Advanced BKVN results in severe tubulo‐interstitial damage and graft failure. Retransplantation after BKVN is associated with good outcomes. Newer treatment modalities are emerging.     

Epstein-Barr virus latency in kidney specimens from transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV) infection is common in immunosuppressed patients and can lead to life threatening lymphoproliferative diseases. Small numbers of cells infected by EBV have been detected in human tissues, transplanted or non-transplanted. Little is known about EBV latency in the allograft kidneys of patients without post-transplant lymphoproliferative disease (PTLD). The aims of this study were to look for the presence of EBV-encoded small RNAs (EBER) in allograft kidneys and to quantify their expression. METHODS: We analysed 62 allograft nephrectomies and 20 native kidneys to determine the presence of EBV; we also quantified its expression and calculated its ratios to CD45 and CD20 cells. The techniques used were: tissue microarray, EBER-1- and 2-specific in situ hybridization and immunohistochemistry. RESULTS: EBER expression was detected in 30.6% of transplanted kidneys and 5% of non-transplanted kidneys. In the positive specimens, a mean of 8.2 cells/1.57 mm(2) expressed the EBERs (range 1-38 cells). The ratios of EBER-positive (+) cells to CD45 or CD20 cells were 1.7 +/- 2.4% (range 0.1-8.1%) and 8.4 +/- 10.9% (range 0.5-34.4%), respectively. No relationship was found between anti-T-cell treatment and EBER expression in the failed allografts. CONCLUSIONS: In failed kidney allografts, a small number of lymphocytes can express EBV latency. The number of EBER+ cells is smaller than in PTLD. Studies of functioning grafts are necessary to better understand the clinical relevance of this expression.     

Epstein-Barr virus infection and immunity in bone marrow transplant recipients

Studies on patients for up to one year following allogeneic, HLA-matched bone marrow transplants have shown no increased incidence of salivary Epstein-Barr (EB) virus secretion and no significant rise in EB-virus-specific antibody titers. EB-virus-specific cytotoxic T cells could be detected in the peripheral blood of all patients by six months posttransplant. For up to one year posttransplantation in vitro EB virus infection of peripheral blood B lymphocytes from the majority of patients leads to an abortive infection followed by cell death, and without the establishment of continuously growing cell lines. This abnormality appeared to be due to patients' monocytes, which formed a defective feeder cell layer in culture, and it could be circumvented by culturing the EB-virus-infected B cells from patients on a feeder layer of x-irradiated adherent cells from normal peripheral blood. These findings may explain the relative lack of EB-virus-associated lymphoma seen in bone marrow transplant recipients when compared with other groups of transplant patients.     

Opportunistic posttransplantation virus infections in renal transplant recipients

Background

Opportunistic virus infection is one of the most common complications in renal transplant (RT) recipients. Cytomegalovirus (CMV) and BK virus (BKV) are important pathogens and each of these infections affects the other. In contrast, there is only limited information on JC virus (JCV) infection and its relation to CMV infection in RT recipients. This prospective study investigated the rates of JCV and CMV infections and their risk factors and correlations.

Methods

We studied 52 RT recipients. JCV and CMV were detected using nested qualitative polymerase chain reaction assays of urine. The clinical characteristics of JCV and CMV infection were compared and risk factors analyzed with the use of binary logistic regression.

Results

JCV and CMV were detected in 40.4% and 34.6% of the RT recipients, respectively. Cyclosporine (CsA) was a risk factor for both JCV and CMV infection (odds ratio [OR] 7.187; P = .002; OR 4.182; P = .021); CMV infection was a risk factor for JCV infection (OR 3.900; P = .039).

Conclusions

JCV and CMV infections are common in RT recipients. CsA is a risk factor for both JCV and CMV infection. JCV infection is related to CMV infection.     

肾移植受者BK病毒的感染特点

Objective To investigate the characteristics of BK virus (BKV) infection in renal transplant recipients. Methods A total of 243 renal recipients from our clinic within 48 months after transplantation were enrolled as the trial group and 82 healthy people as the control group. Urine and peripheral blood samples of these two groups were harvested for urinary sediment BKV cytology by Decoy cell counting and BKV DNA by real-time PCR. Results The positive rates of urinary Decoy cell, BKV viruria and viremia were 35.4%, 36.6% and 16.9% in trial group, and 4.9%, 20.7% and 2.9% in control group, respectively. In trial group, the medians of urinary Decoy cell, urinary BKV and peripheral blood BKV were 6/10 HPF, 1.00×104 copy/ml and 6.87×103 copy/ml respectively, while in control group, they were 2/10 HPF, 1.10×104 copy/ml and 2.24×1(3 copy/ml. Compared with the healthy people, the positive rates and the levels of BKV DNA in urine and peripheral blood of recipients were significantly higher. The amount of urinary Decoy cells was positively correlated to urinary BKV load (r=0.636, P＜0.01). Conclusions BKV replication is easier to happen in renal recipients as compared to healthy people. Counting of urinary Decoy cells is convenient, useful and sensitive to evaluate BK viruria and viremia in renaltransplant recipients. BKV DNA detection in urine and peripheral blood can be used to screen the evidence of BK reaction in order to prevent irreversible graft damage by BKV.[ Key words ] Kidney transplantation; BK virus; Kidney diseases; Decoy cells     

肾移植受者BK病毒的感染特点

目的 探讨肾移植受者BK病毒（BKV）的感染特点。 方法 于我院门诊选取肾移植术后48个月内的患者共243例作为试验组,同时选取门诊健康体检者82例作为对照组。采集上述2组的血、尿标本,行BKV尿沉渣细胞学计数与实时荧光定量PCR检测。 结果 试验组受者的尿Decoy细胞、BKV尿症与BKV血症的阳性率分别为35.4 %、36.6%和16.9%;对照组分别为4.9%、20.7%和2.9%。试验组受者的尿Decoy 细胞阳性者Decoy细胞中位数水平为6个/10 HPF,BKV DNA阳性者尿液和外周血BKV中位数水平分别为1.50×104拷贝/ml和6.87×103拷贝/ml;对照组分别为2个/10 HPF,1.10×104拷贝/ ml和2.24×103拷贝/ml。与健康者相比,肾移植术后试验组BKV DNA阳性率及水平明显升高（P < 0.01）。肾移植受者的尿液Decoy 细胞计数与尿液BKV含量呈正相关（r = 0.636,P < 0.01）;尿Decoy大量组（＞10个/10 HPF）的血BKV DNA阳性率及水平显著高于少量组（1～5个/10 HPF）（P < 0.05）。 结论　肾移植受者较健康人群易发生BKV再活化。定量尿沉渣细胞学检测简单、易行、敏感,可以作为BKV活化的指标,预测病毒尿症及病毒血症。此外,也可检测血、尿BKV DNA,以了解病毒活化情况和筛查BKV相关的移植肾肾病。     

肾移植受者BK病毒的感染特点

Objective To investigate the characteristics of BK virus (BKV) infection in renal transplant recipients. Methods A total of 243 renal recipients from our clinic within 48 months after transplantation were enrolled as the trial group and 82 healthy people as the control group. Urine and peripheral blood samples of these two groups were harvested for urinary sediment BKV cytology by Decoy cell counting and BKV DNA by real-time PCR. Results The positive rates of urinary Decoy cell, BKV viruria and viremia were 35.4%, 36.6% and 16.9% in trial group, and 4.9%, 20.7% and 2.9% in control group, respectively. In trial group, the medians of urinary Decoy cell, urinary BKV and peripheral blood BKV were 6/10 HPF, 1.00×104 copy/ml and 6.87×103 copy/ml respectively, while in control group, they were 2/10 HPF, 1.10×104 copy/ml and 2.24×1(3 copy/ml. Compared with the healthy people, the positive rates and the levels of BKV DNA in urine and peripheral blood of recipients were significantly higher. The amount of urinary Decoy cells was positively correlated to urinary BKV load (r=0.636, P＜0.01). Conclusions BKV replication is easier to happen in renal recipients as compared to healthy people. Counting of urinary Decoy cells is convenient, useful and sensitive to evaluate BK viruria and viremia in renaltransplant recipients. BKV DNA detection in urine and peripheral blood can be used to screen the evidence of BK reaction in order to prevent irreversible graft damage by BKV.[ Key words ] Kidney transplantation; BK virus; Kidney diseases; Decoy cells     

Kaposi's visceral sarcoma in liver transplant recipients

We report three cases of Kaposi's sarcoma after orthotopic liver transplantation performed for cirrhosis related to hepatitis C virus (one case), ethanol (one case), or both (one case). All patients displayed disease within the first year after liver transplantation, and only in one case was the diagnosis obtained before the patient died. All three patients were on tacrolimus-steroid therapy, and in one case mycophenolate mofetil was added to treat acute persistent rejection.     

Clinicopathological aspects of 18 Kaposi's sarcoma among 1055 Greek renal transplant recipients

The incidence of Kaposi's sarcoma (KS) in transplant recipients is 400-500 times greater than that in the general population, and is rising within the transplant population. In this study, between March 1983 and December 2001, 1055 cases were recorded where KS developed in 18 patients (1.7%) who were treated with AZA + CsA + MP, MMF + CsA + MP, MMF + Tac + MP, CsA + MP, or AZA + MP therapy (AZA, azathioprine; CsA, cyclosporine A; MP, methylprednisolone; MMF, mycophenolate mofetil; Tac, Tacrolimus). In the present study, 18 renal transplant recipients who developed KS and were followed and analyzed. Analysis revealed that a continuous state of immunodeficiency is important for the development of KS. Prognosis in patients with KS limited to the skin is favorable, while visceral involvement is associated with high mortality. Transplant function is well preserved in most of the cases. The association, previously described, between human herpesvirus 8 (HHV8) and transplant-associated KS also exists in the studied population.