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Background: Reactivation of cytomegalovirus (CMV) is typically considered harmless as long as the immune system remains unaffected by medications or other factors. CMV reactivation may occur as a result of acute graft-versus-host disease of Grades II to IV. One possible factor contributing to this risk is the rise in the number of donors who lack genetic similarities or relationships. We hypothesized that the anti-CMV IgG level before transplantation could potentially serve as an indicator of the likelihood of CMV reactivation following hematopoietic cell transplantation., Methods: We examined a cohort of young individuals who underwent allogeneic HCT between 1998 and 2022 to evaluate the occurrence of CMV reactivation. The patients were divided into 2 time periods: 1998 to 2016 (comparison group) and 2017 to 2022 (intervention group)., Results: Between 1998 and 2016, 292 patients underwent hematopoietic HCT. Recipients from 2017 to 2022 experienced a slightly higher risk of CMV reactivation than those from 1998 to 2016. The comparison of prophylactic and preemptive medication showed no significant difference between the periods (P = .32). Patients treated from 1998 to 2016 experienced a 23% decrease in the risk of symptomatic CMV reactivation and related illnesses compared to those treated from 2017 to 2022 (P = .08 and .15, respectively)., Conclusions: Our study showed that the intervention group had more symptomatic CMV reactivations. Various factors may contribute to this, including CD19-directed immunotherapy and the CMV status of the recipient before transplantation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV), the most common opportunistic infection of kidney transplantation (KT), is preventable by prophylactic and preemptive antiviral drugs in CMV-immunoglobulin (Ig)G-positive donors. Our preemptive therapy optimized immunosuppressive doses based on mixed lymphocyte response (MLR) results, regardless of preoperative CMV-IgG serostatus pairing. This study used the MLR to compare the anti-donor T-cell responses between CMV antigenemia-positive and -negative cases., Methods: One hundred patients underwent KT using a cyclosporine (CsA)-based immunosuppressive regimen at Hiroshima University Hospital. CMV antigenemia-positive cells were defined as 4/50,000 CMVpp65-positive cells. T-cell responses to allo-antigens were measured using MLR assays to evaluate patients' anti-donor immune reactivity. After analyzing the proliferation of CD4 + and CD8 + T-cell subsets, the stimulation indices of CD4 + or CD8 + T cells were quantified. The study used no prisoners, and the participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul., Results: Forty-three patients tested positive for CMV antigenemia within 3 months after KT. No significant differences were found between the CMV antigenemia-positive and -negative groups in the stimulation indices for CD4 + and CD8 + T-cell responses to anti-donor stimulation. However, T-cell responses to third-party stimuli during the postoperative month 1 were significantly less in the CMV antigenemia-positive than -negative group., Conclusion: Anti-donor T-cell responses are not necessarily attenuated during CMV infection in KT recipients. In CMV-infected KT recipients, caution should be exercised against inadvertent dose reduction of immunosuppressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: In this study,we investigated the presence of cytomegalovirus (CMV) infection in kidney transplanted children and its effect on kidney dysfunction., Material and Methods: One hundred thirty-five pediatric renal transplant patients were included in this study. The presence of CMV infection, CMV risk status, and other clinical features of the patients were evaluated retrospectively., Results: Fifty-three percent of all patients and 68.8% of patients with CMV were male. The mean age was 12 years in all patients and CMV groups. According to the CMV risk classification, 40.9% of the patients with CMV infection/disease were in the high-risk group (CMV D+R-). In CMV risk groups, the presence of CMV infection/disease was similar. Cold ischemia time, male sex (patients and donors), deceased donor, higher HLA-mismatches, and cumulative antithymocyte globulin dose were found as risk factors for CMV infection/disease. Acute rejection/graft failure was observed in 27% of all patients. CMV infection has no effect on rejection/graft failure and survival., Discussion: The frequency and risk factors of CMV in renal transplant children in our study were consistent with the literature., Conclusions: CMV infection was found in one-fifth of our patients and the majority (71.9%) of them developed infection in the first 6 months. In one-third of our patients acute rejection/graft failure was observed. There was no effect of CMV infection on rejection/graft failure and survival in pediatric patients with proper and effective treatment., (Copyright © 2020. Published by Elsevier Inc.)

Cytomegalovirus (CMV) is the most common viral pathogen in kidney transplant recipients (KTRs), and CMV disease impacts patient and graft survivals. CMV-specific CD8 T cell mediated-immunity (CMI) may help to assess the risk of CMV disease and to adapt preventive treatment strategies. High-risk KTRs with CMV seropositive donors/seronegative recipients (D+/R-) were prospectively monitored after CMV prophylaxis discontinuation and during the first year post transplant for CMV viremia (World Health Organization standardization) and CMI (QuantiFERON-CMV). We analyzed the ability of CMI test to predict either subsequent spontaneous viral clearance or CMV disease after prophylaxis discontinuation in patients with asymptomatic viremia. We enrolled 12 consecutive (D+/R-) KTRs. Eleven patients developed a viremia during follow-up, but 7 of them (64%) exhibited a spontaneous viral clearance. At viremia onset, 6 of 11 patients (55%) had a positive CMI test, and all of them (6 of 6, 100%) had subsequent spontaneous viral clearance, compared with only 1 of 5 patients (20%) displaying a nonreactive CMI (P = .02). This latter patient exhibited a positive CMI test 15 days after viremia onset. Four of the 11 patients (36%) developed a CMV disease, and their CMI either remained nonreactive or became positive only after antiviral treatment. We conclude that D+/R- KTRs with asymptomatic viremia after prophylaxis discontinuation may benefit from QuantiFERON-CMV to predict when positive for the spontaneous viral clearance or when persistently negative or the development of a CMV disease., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV) is the most common viral infection after kidney transplantation and is associated with significant morbidity and mortality. Recent studies showed that CMV-specific CD8+ T cells play the crucial role in protection against CMV. The Quantiferon-CMV (QF-CMV) is an interferon gamma (IFN-γ) release assay (IGRA test) that measures the IFN-γ response to a range of T-cell epitopes of CMV. In the present study, we analyzed the clinical utility of QF-CMV assay to predict CMV infection in kidney transplant recipients and evaluated if reactive result in QF-CMV test could be predictor of the duration of treatment., Methods: We studied 75 renal transplant recipients who had IGRA testing just before transplantation. The donor and recipient variables were reported from the clinical history. The variables related to transplantation were collected from transplantation process data and included CMV infection or disease, CMV treatment, and immunosuppressive treatment. Laboratory variables were C3-C4 complement fractions and DNA quantification of CMV., Results: Fifty percent of patients had CMV infection, and 35.9% had CMV disease. The time of negativization of CMV DNA was 56.61 ± 23.5 days. Univariate analysis related to CMV infection only showed a statistically significant relation with thymoglobulin treatment (P = .001). Statistically significant variables in relation with CMV infection incidence were donor serology (P = .044) and thymoglobulin treatment (P = .004). The probability of CMV infection was lower with positive IGRA assay (P = .025)., Conclusion: We found that IFN-γ response measured by QF-MV is a protective factor against CMV infection in post-transplantation kidney recipients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection., Methods: Seventeen patients on pre-emptive antiviral therapy and CMV quantitative polymerase chain reaction (qPCR) ≥500 copies/mL (first episode after transplantation) were assessed using ELISpot and divided into Weak (9 patients with baseline ELISpot <25 spot-forming colonies [SFCs]/200,000 peripheral blood mononuclear cells [PBMCs]) and Strong Responders (8 patients with baseline ELISpot ≥25 SFCs/200,000 PBMCs). CMV-specific T-cell response, infection severity, viral load, and antiviral therapy were prospectively recorded and compared between groups at 1, 2, and 24 months of follow-up., Results: Demographic and transplant characteristics of Weak and Strong Responders were similar. No episodes of CMV disease were observed. Weak Responders were more likely to experience CMV syndrome (56% vs 36.5%) and late virus reactivation (56% vs 25%) than Strong Responders. Weak Responders showed higher baseline median viral loads (19,700 vs 9265 copies/mL) and needed antiviral therapy for longer (179 vs 59.5 days). T-cell response showed 2 main patterns: early and delayed., Conclusions: ELISpot provides prognostic information about infection severity, risk of late reactivation, and response to therapy. Randomized trials, evaluating the need for antiviral therapy in kidney transplant recipients with asymptomatic infection and effective virus-specific T-cell immune response, are warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Kidney transplant patients with D+/R+ serology can be treated with either prophylaxis or preemptive valganciclovir. The older transplant population suffers severe immunosenescence, especially patients with latent cytomegalovirus (CMV) infection (R+). They are more likely to develop indirect CMV effects. Likewise, many patients have significant cardiovascular comorbidity, which makes them more sensitive to these indirect effects. The aim of this study was to evaluate the incidence of CMV viremia and indirect effects on survival, comparing prophylaxis (V) against preemptive (P) valganciclovir in an older kidney transplant population., Methods: We analyzed the data of 233 recipients from 2002 (age, >55 years; D+/R+) with ≥6 months of follow-up. The patients were divided into 2 groups: 167 (71.7%) in the V group and 66 (28.3%) in the P group., Results: The incidence of CMV infection in the P group was 32% versus 6% in V group. Patients with CMV viremia showed worse survival values than patients without viremia (log rank P = .031). Five-year survivals were 74% vs 88%, respectively. Cox regression showed that the adjusted effect of CMV infection on overall survival was a significant risk (hazard ratio [HR], 2.07; 95% CI, 1.003-4.29). Patients with CMV viremia showed worse cardiovascular survival than patients without viremia, with 5-year survivals of 79% vs 94%. Cox regression showed that the adjusted effect of CMV infection was a significant risk (HR, 2.62)., Conclusions: CMV infection has a detrimental effect on the survival of older patients. Valganciclovir prophylaxis induces a protective effect against CMV infection and could improve survival of older patients with cardiovascular comorbidities., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Specific anticytomegalovirus (anti-CMV) intravenous immunoglobulin (IVIG) has the potential to influence the immune response, but its complex mode of action has not been well evaluated., Methods: An immunologic study of 6 CMV-seronegative heart transplant patients receiving anti-CMV prophylaxis with the use of ganciclovir and CMV-IVIG (150 mg/kg within 24 hours after transplantation and 100 mg/kg on days 2, 7, 14, 22, 35, 56, and 77 after transplantation) was performed in a single center. Lymphocyte subsets were evaluated by means of 4-color flow cytometry at the time of inclusion in the waiting list and at 3 months after transplantation., Results: High-risk heart recipients receiving CMV-IVIG showed a clear reduction in the frequency of activated CD4+CD38+DR+ T-helper cells at 3 months after transplantation compared with a group of 27 untreated control subjects who received only anti-CMV prophylaxis with the use of ganciclovir. In this study, an increase of CD19+CD27-IgM+IgD+ naïve B cells was also observed in seronegative recipients after prophylaxis with the use of CMV-IVIG but not in control subjects. None of the CMV-IVIG-treated recipients developed acute cellular rejection during the 1st 6 months after transplantation., Conclusions: The immune modulation of activated CD4+ lymphocyte and of naïve B-cell subsets after CMV-IVIG use should be further evaluated in future prospective studies with higher numbers of patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Immune monitoring of cytomegalovirus (CMV) - specific T-cells responses has become an additional tool in the CMV risk assessment of kidney transplant recipients (KTRs). Some data demonstrated a potential use of QuantiFERON-CMV assay (QF-CMV) in stratifying CMV risk before transplantation, at the end of prophylaxis and during pre-emptive strategy. High risk for CMV disease was also reported in KTRs with indeterminate QF-CMV results in which both mitogen and CMV antigen responses were absent. Twenty-five KTRs in the first year after kidney transplantation (KT), including 17 KTRs after CMV infection treatment (CMV-KTR), were studied by QF-CMV assay. Positive QF assay (QF+) was present in 16 of 25 (64%) of KTRs, negative (QF-) in 5 of 25 (20%), and indeterminate (QF0) in 4 of 25 (16%). The QF0 patients, in comparison to the combined group of QF+ and QF-, presented an increased incidence of CMV disease (4 of 4 [100%] vs. 7 of 21 [33.3%]; P < .05) and severe infectious complications such as sepsis, and systemic mycosis (4 of 4 [100%] vs. 6 of 21 [29%]; P < .02). Of 17 CMV-KTRs, 11 of 17 (64.7%) were QF+, 2 of 17 (11.8%) were QF-, and 4 of 17 (23.5%) were QF0. The incidence of CMV disease and severe infectious complications was not different among these groups. CMV-KTRs with interferon-γ <3.5 IU/mL vs. >3.5 IU/mL in mitogen tube, irrespective of QF-CMV status, showed an increased incidence of CMV disease (8 of 9 [88.9%] vs. 3 of 8 [37.5%]; P < .05) and severe infectious complications (8 of 9 [88.9%] vs. 2 of 8 [25%]; P < .02). In conclusion, indeterminate result of QF-CMV or interferon-γ <3.5 IU/mL in mitogen tube seems to be related to impaired immunity. The QF-CMV assay appears to be a useful tool in clinical practice, identifying the group of KTRs with increased risk of infectious complications who may benefit from immunosuppression reduction and maintenance of antiviral prophylaxis., (Copyright © 2016. Published by Elsevier Inc.)

Background: Cytomegalovirus infection (CMV) is prevalent in kidney transplant patients. Which level of CMV viral load should be accepted as the gold standard for CMV infection diagnosis is a relatively unsettled issue., Methods: Seventy-three kidney transplant patients (mean age = 35.97 ± 14.07 years, 39 male and 34 female) entered this retrospective study. The area under the curve (AUC) of the receiver operative curve (ROC) characteristics was used to define which level of CMV viral load results in the most sensitivity and specificity for different clinical and para clinical parameters differing infected and non-infected patients. Quantitative real-time polymerase chain reaction (TaqMan method) was used for measuring CMV viral load. Written consent was obtained from all patients., Results: Platelets, compared with the other clinical and para-clinical parameters, had the strongest correlation with CMV viral load in kidney transplant patients (r = -.314, P = .007). There was no correlation between CMV viral load and other laboratory parameters including clinical manifestation. Choosing a threshold of more than 10,000 copies/mL of CMV viral load for defining CMV infection resulted in significance for differing in both white blood cell and platelet count between infected and non-infected patients (AUC = .68, P = .023; AUC = .70, P = .014, respectively)., Conclusions: Accepting a CMV viral load threshold of more than 10,000 copies/mL as CMV infection has the most sensitivity and specificity for predicting both white blood cell and platelet counts in kidney transplant patients. No CMV viral load threshold as the gold standard for CMV infection diagnosis has the discriminatory power for differing clinical and para-clinical parameters other than platelet and white blood cell count between presumably infected kidney transplant patients and those not infected., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Cytomegalovirus (CMV) infection is known to be the most frequently viral infection among patients after liver transplantation. This is especially true in pediatric living-donor liver transplantation because the recipients have often not been infected with CMV and postoperative primary infection with CMV frequently occurs., Patients and Methods: Of 93 patients who underwent pediatric liver transplantation at our department, 33 patients (36.3%) were diagnosed with CMV infection using the antigenemia method (C7-HRP). Retrospective review and statistical analysis were conducted to confirm risk factors of post-transplantation CMV infection., Result: Positive lymphocytes were diagnosed between postoperative days 8 and 111 after transplantation. Ganciclovir or foscavir were administrated to 21 patients. The other 10 patients who had one positive lymphocyte were observed and the cell disappeared on follow-up examination. We did not observe any cases of positive lymphocytes with C7-HRP in patients who received a graft from a CMV antibody-negative donor. Independent predictors associated with CMV infection in the multivariable analysis were administration of OKT3 and grafts from CMV antibody-positive donors., Conclusion: In CMV infection after pediatric liver transplantation, cases with CMV antibody-positive donors and with OKT3 administration for acute rejection are considered high risk, and cases with CMV antibody-negative donors are considered low risk., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Currently, the long-term advantages of having a pancreas transplantation (PT) are debated, particularly in patients receiving pancreas after kidney (PAK) allografts. The United Network for Organ Sharing (UNOS) requires that a transplant center perform a minimum number of PT per year to remain an active PT center. The long-term outcomes and challenges of PAK in small pancreas transplant centers are not well studied., Methods: In this retrospective analysis, we report short- and long-term outcomes in a small center performing 2-9 PT annually., Results: Forty-eight PT (25 simultaneous pancreas and kidney transplantation [SPK], 23 PAK) were performed in our center. Donor and recipient demographics were similar in both groups. All suitable local donors were used for SPK. All organs for PAK transplantation were imported from other UNOS regions. Mean follow-up was 61 ± 46 and 74 ± 46 months for SPK and PAK, respectively. Patient and graft survival rates were similar in SPK and PAK groups and better than the reported national average. Four patients (11%) died (1 due to trauma, 1 brain lymphoma, 1 ruptured aneurysm; and 1 unknown cause). Two patients (4%; 1 SPK, 1 PAK) lost their grafts because of thrombosis on postoperative days 3 and 5 in 2002. No graft thrombosis occurred since 2002. Seven patients (15%) required reoperation (4 for bleeding, 2 anastomotic leaks, 1 small bowel perforation). Two patients (4%) developed post-transplantation lymphoproliferative disease. Five patients (11%) experienced cytomegalovirus antigenemia which responded well to antiviral therapy., Conclusions: Compared with outcomes for diabetic patients on dialysis, current SPK and PAK short- and long-term results are favorable even in a small PT center. Therefore, unless there is a contraindication, PT should be offered to all type 1 diabetic patients with end-stage renal disease at the time of kidney transplantation or afterward., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Human herpesvirus (HHV) 5 and 6 remain latent after primary infection and can be reactivated after immunosuppression for organ transplantation. An association between HHV-5 and HHV-6 has been reported in liver transplant patients. The coinfection is associated with clinical manifestations and graft dysfunction., Objective: The aim of this study was to monitor herpesviruses in liver transplant recipients to better understand issues involving coinfection with HHV-5/6 and correlations with acute cellular rejection episodes and bacterial infections., Methods: Forty-five adult liver transplant patients of median age 47 years (range, 18-66), gave blood samples and liver biopsies in the first 6 months after their surgeries. Viremia was detected with the use of nested PCR and antigenemia; the Banff classification was used to detect allograft rejection., Results: IgG positive for HHV-5 was observed in 94% of subjects whose main indication (67%) for transplantation was hepatitis C. Twenty-three (51.1%) displayed cytomeg virus (CMV) infections and 12 (26.7%) HHV-6 infection. There were 6 patients (13.3%) with HHV-5/6 coinfections. Eighteen of the 23 patients had CMV disease, showing a strong correlation between a positive test and CMV disease; 6 displayed an acute cellular rejection episode in the same period (χ(2) = 6.62; P < .03). Four out of 6 patients who displayed coinfections (HHV-5/6) had concomitant bacterial infections; 3/6 experienced graft rejection episodes. During follow-up, 1 patient had HHV-6 infection diagnosed as encephalitis followed by fever on the 24th day after surgery. The median 32 days for HHV-6 detection by nested PCR positivity was shorter than 38 days for HHV-5., Conclusions: HHV-5/6-infected patients displayed more allograft rejection episodes, coinfections, and concomitant bacterial infections, besides an higher risk for CMV disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Cytomegalovirus (CMV) can reactivate causing serious clinical problems during immunosuppression. CMV-specific CD8(+) T cells play an important role in the control of CMV reactivation. Using pentameric major histocompatibility complex (MHC) peptide complexes, we investigated cellular immune responses to CMV among healthy individuals and kidney transplantation recipients in Korea, which is an endemic area of CMV infection., Materials and Methods: Analysis of CMV-specific T cells was performed on 28 healthy individuals and 40 recipients who bore human leukocyte antigen (HLA)-A2 or -A24. CMV pp65 pentamer-binding cells incubated with various monoclonal antibodies were measured by four-color flow cytometry., Results: Detectable levels of pentamer(+) CD8(+) T cells were present in 109/139 samples (78.4%) that stained with the A*02NLV-pentamer, while 15/67 samples (22.4%) stained with the A*24QYD-pentamer (P < .01). Among patients with HLA-A2, 22/24 (91.7%) samples showing positive CMV antigenemia revealed detectable pentamer(+) CD8(+) T cells, while 87/115 (75.7%) displaying negative CMV antigenemia had detectable pentamer(+) CD8(+) T cells (P = .04). There was no significant difference in percentages of pentamer(+) CD8(+) T cells between patients who did versus who did not experience episodes of CMV infection. The subpopulation of CMV-specific CD8(+) T cells in transplantation recipients was evaluated using phenotypic markers; memory cells comprised the majority of the CMV-specific CD8(+) T-cell population., Conclusion: The A*02NLV-pentamer complex was useful to monitor CMV-specific T cells. However, MHC pentamer-based techniques did not provide a clear distinction between patients who are or are not at risk for CMV infection., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV) is endemic throughout the world, affecting most of the population, but the seroprevalence of CMV is known to vary among countries. CMV causes a mild infection in persons with intact immunity; however, CMV infection in organ transplantation is associated with significant morbidity and mortality. The present retrospective study was designed to evaluate the age-, gender-, and blood group-adjusted CMV seroprevalence among solid organ donors, representing fairly the overall Hungarian population (according to Hungarian Central Statistic Institute). This information is important for calculating risk-factors for CMV-seronegative recipients. No nationwide estimates of CMV seroprevalence in Hungary (as a representative of Eastern Middle Europe) have been published yet., Methods: We investigated 2070 organ donors for CMV seroprevalence by measuring the CMV-specific immunoglobulin G. The donors were divided into 3 age groups (2-20, 21-50, and 51-70 years old). A study was also conducted on a fourth group consisting of 200 residents from an old age home. CMV seroprevalence differences were searched according to age-, gender- and blood-group distribution., Results: The CMV seroprevalence of organ donors is 85% and of all investigated persons is 86%. The age-specific prevalence increases, starting from 72% in the first group to 99% in the fourth group. Seroprevalence of females was found to be significantly higher than of males (P=.0001)., Conclusion: We have shown that the overall CMV seroprevalence in the Hungarian population is moderately high at 86%. The opportunity for CMV-seronegative recipients to get a graft from a seronegative donor is statistically only 2%. The seroprevalence of the youngest age group is 72% and so it can be concluded that the Hungarian population acquires the infection mainly in childhood or in the early adulthood. Female gender is a risk factor for CMV infection. This fact must be taken into consideration during the planning of patients' follow-up, prophylaxis, and therapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Human herpesvirus (HHV)-6, HHV-7, and cytomegalovirus (CMV) that remain latent after primary infection can be reactivated during immunosuppression following organ transplantation in liver transplant recipients. The aim of this study was to monitor active infections for HHV-6, HHV-7, and CMV among adult liver transplantation recipients using antigenemia detected by an immunoperoxidase staining. Twenty-eight adult liver transplant patients were monitored using antigenemia in blood samples obtained at the time of transplantation, as well as weekly in the first month and once a month for 6 months. Of these patients, 28.5% showed positive CMV antigenemia; 39.2%, HHV-6 antigenemia; and 14.2%, HHV-7 antigenemia. The detection of the three viruses was considered to be independent of one another (P>.05). The results described above showed that few patients remain free of beta herpesviruses after liver transplantation. Most patients were infected sequentially and not concurrently. Antigenemia has been considered useful to detect active HHV-6 and HHV-7 infections. Antigenemia can be more efficiently interpreted when compared with polymerase chain reaction results, although other studies are necessary to establish the reference of HHV-6 and HHV-7 antigenemia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In lung transplant recipients, cytomegalovirus (CMV) has been associated with direct ie, organ and systemic infection/disease, and indirect effects, including predisposition to develop acute rejection episodes and chronic allograft dysfunction. Cellular immune responses have been demonstrated to play a role in the control of CMV replication. We evaluated CMV-specific cellular responses among lung transplant recipients associated with the onset of organ infection/disease. Cellular responses were evaluated by an Elispot assay of 48 specimens from 24 patients. All samples were evaluated beyond 1 year after transplantation; CMV DNA was concomitantly detected in bronchoalveolar lavage (BAL) and whole blood specimens. Each patient received a combined prolonged antiviral prophylaxis with CMV Ig for 12 months and gancyclovir or valgancyclovir for 3 weeks after postoperative day 21. Nine patients (37.5%) showed transient or persistent CMV nonresponses including donor-recipient negative serologic matching in 2 cases. Positive CMV DNA results were observed in 18/48 BAL specimens (37.5%) from 12 patients (50%). A viral load of >10(4) copies/mL was observed in only 3 cases, 2 of whom were positive also on whole blood. Among these 3 patients, 2 were responders and BAL (as well as whole blood) specimens collected subsequently were negative for CMV DNA; 1 nonresponder patient exhibited a viral load of 426,492 copies/mL BAL (DNAemia, <2,000 copies/mL), developed CMV pneumonia (confirmed by histopathology and immunohistochemistry) and died within 28 days. The prevalence of CMV DNA positivity on BAL did not differ in relation to the immune response; the mean viral load on BAL showed significantly higher results among nonresponders than responders, namely, 1.4 × 10(5) ± 2.4 × 10(5) copies/ml versus 7.9 × 10(3) ± 1.4 × 10(4) (P=.02). Evaluation of CMV-specific cellular immune responses by in vitro immunologic monitoring complements virologic monitoring, helping to identify lung transplant recipients at risk of developing organ infection/disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Cytomegalovirus (CMV) is a β-herpesvirus. CMV infections are a common complication contributing to morbidity and mortality after liver transplantation. Among organ transplant recipients, CMV can reactivate from latency during the first 6 months. This prospective study performed from February 2008 to December 2009 examined liver transplant recipients during the first 6 months. Two methods were performed to detect CMV infections: antigenemia (AGM) and nested (PCR). Ninety-four patients, including 72 men (76.6%) and 22 women (23.4%) underwent liver transplantation during this period. We analyzed 575 samples including 465 for AGM and PCR. Forty-three (9.25%) showed positive AGM as detected 2 to 179 days posttransplantation with a mean of 50 days and a median of 35 days, and 93/465 (20%) showed positive PCR at 0 to 186 days posttransplantation with a mean of 31 days and a median of 38 days. Among the 43 antigenemia patients, 38 samples were positive for up to 5 cells 18 of which were PCR-positive. Five samples were positive with more than 5 cells, including 3 that were PCR-positive. Only 4.51% had AGM and were PCR-positive in the same sample. Despite only 9.25% (43/465) showing AGM, the current study suggested the utility of routine monitoring to detect early CMV infection among liver transplantation patients seeking to reduce morbidity and mortality., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Infection with cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunosuppressed patients, including organ and bone marrow transplant recipients. The majority of CMV disease is caused by reactivation of alatent infection rather that by newly acquired virus. Many techniques have been currently available to aid in the diagnostics of CMV disease. In this report we performed a prospective evaluation of Quantiferon-CMV assay (Cellestis) to determine whether the test is predictive of CMV disease. CD8+ T-cell CMV-specific immunity was assessed in a longitudinal cohort of 14 kidney transplant recipients. According to our data, subjects with higher cellular immune response measured with Quantiferon test had a lower risk of manifestation of CMV infection than subjects with lower responses. Despite the small number of patients and large intra- and interindividual variability of the data in the study, we observed the Quantiferon-CMV assay to be a sensitive specific test to detect a virus-specific T-cell response. We propose that this assay in combination with viral DNA load estimates may prove to be useful to stratify patients at risk of CMV disease., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Fifty percent of allogeneic stem cell recipients develop cytomegalovirus (CMV) infection in the first 100 days posttransplantation. Various methods have been used to determine CMV infections, including antigenemia assay and real-time polymerase chain reaction (RT-PCR). Although antigenemia assay has been used more frequently, this technique is less sensitive than RT-PCR. In contrast, RT-PCR has a low positive predictive value for CMV end-organ disease. Cytomegalovirus infections were analyzed in 41 peripheral blood samples from allogeneic stem cell recipients using both antigenemia assay and RT-PCR; results were discordant in 36.6% of patients. Although the antigenemia assay detected CMV replication in 29.2% of cases, RT-PCR was positive in 65.8%. In 83.3% of patients, results detected using the antigenemia assay were delayed by a median (range) of 5 (2-20) weeks compared with positive RT-PCR results. Within the first 100 days posttransplantation, higher levels of viral replication measured using RT-PCR were observed in patients with vs without antigenemia. In addition, in patients with antigenemia, viral load was significantly higher before day 100 than after (P=.01 and P=.008, respectively) compared with those without antigenemia., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: A prospective study was performed in kidney transplant patients at risk of developing cytomegalovirus (CMV) infection (CMV D+/R-). They were treated with valganciclovir (VGC) for 3 months as prophylactic therapy. The aim was to determine the safety and efficacy of prophylactic therapy with VGC., Methods: Antigenemia and/or polymerase chain reaction CMV was routinely performed every 2 weeks up to month 3, monthly to month 6, and every other month until the end of the first year posttranplantation, as well as when clinically indicated., Results: From July 2007 to April 2010, 366 renal transplantations were performed at our center, including 34 (9%) high-risk patients for CMV infection. The median age was 47 years; 19 were males and 15 females. Twelve (35%) patients developed CMV infections: 10 (34%) gastrointestinal disease and 3 viral syndromes. The timing of the clinical manifestations was 16% (3/12) between months 1 and 3, 75% (8/12) between months 4 and 6, and 8% (1/12) in month 9 posttransplantation., Conclusion: Treatment with intravenous ganciclovir followed by oral VGC was successful in all patients. No opportunistic infections or allograft rejection were observed; only 1 patient developed thrombocytopenia as an adverse event to VGC., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Epstein-Barr virus (EBV) infections, associated with posttransplant lymphoproliferative disorder (PTLD) are known to develop in cytomegalovirus (CMV)-infected transplant recipients due to the indirect effects of CMV. This study evaluated risk factors for PTLD among pediatric liver transplant recipients with CMV infections. We reviewed the medical records of 119 patients

Cytomegalovirus (CMV) infection is not only a common complication after liver transplantation (OLT), but also a significant contributing factor to morbidity and mortality. We investigated risk factors for CMV syndrome and tissue-invasive CMV disease in CMV antigenemia patients after OLT in a CMV endemic area. CMV antigenemia was regarded to be >1 positive CMV pp65 antigen positive cell per 400,000 white blood cells. We examined the epidemiology, clinical characteristics, and laboratory findings of liver transplant patients with CMV syndrome and tissue-invasive CMV disease. The incidence of CMV syndrome among patients with CMV antigenemia was 10.5% (37/353) and that of tissue-invasive CMV disease, 3.1% (11/353). Upon multivariate analysis the risk factors for CMV syndrome and tissue-invasive CMV disease were infection, low albumin level, high total bilirubin content, and high CMV peak titer. The 1-y, 2-y, and 3-year survival rates of subjects without CMV syndrome were 96.2%, 85.4% and 82.2% versus without tissue-invasive CMV disease, 86.9%, 83.0%, and 80.1%, or 70.3%, 56.1% and 51.8% for CMV syndrome or 72.7%, 62.3%, 49.9% for tissue-invasive CMV disease. The survival curve of patients without were superior to those with CMV syndrome (P=.000). Because OLT recipients had risk factors such as infection, low albumin level, high total bilirubin content, and high CMV peak titer, they were carefully monitored and aggressively managed due to the poor survivals of patients with CMV syndrome., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV) is a major cause of graft failure and posttransplantation mortality in intestinal/multivisceral transplantation. CMV infection exhibits a wide range of clinical manifestations from asymptomatic infection to severe CMV disease. STUDY'S PURPOSE: The purposes of this study were to assess the utility of measuring CMV-specific cellular immunity in bowel/multivisceral transplant recipients and to provide additional information on the risk of infection and development of CMV disease., Methods: We studied 10 bowel/multivisceral transplant recipients to investigate the kinetics of CMV infection using real-time polymerase chain reaction (on blood and biopsy tissue samples) and CMV-specific T-cell reconstitution by Enzyme-linked ImmunoSPOT Assay (ELISPOT) that enumerates Interferon-gamma-secreting CMV-specific T cells upon in vitro stimulation with viral antigens (pp65 and IE-1)., Results: All patients were seropositive for CMV. According to the pattern of T-cell reconstitution occurring either within the first month after transplantation or later, patients were classified as early (n = 7) or late responders (n = 3). Clinically, early responder patients (3/7; 43%) experienced asymptomatic or mild CMV infections, whereas all late responders (3/3; 100%) developed moderate or severe CMV disease. A reduction in mean and peak CMV viral load was observed in early responders, whereas the onset time of infection did not differ significantly between early and late CMV responders., Conclusions: A good and early reconstitution of CMV-specific T-cell immune responses after transplantation is a critical determinant in controlling CMV infections. Simultaneous monitoring of CMV infection and CMV-specific T-cell immunity predicts T-cell-mediated control of CMV infection.

Cytomegalovirus (CMV) is an important pathogen in organ-transplant recipients. There have been frequent reports of CMV-induced adrenal insufficiency in patients with human immunodeficiency virus infection. Herein, we report CMV-induced renal insufficiency in a renal transplant recipient. A 24-year-old woman had gradual onset of weakness, anorexia, nausea, hypotension, and skin hyperpigmentation at 5 months after renal transplantation. The immunosuppression regimen included cyclosporine, mycophenolate mofetil, and corticosteroid (prednisolone, 5 mg/d). Recent history included acute CMV infection, which was treated with ganciclovir. Basal serum cortisol concentration was 4 microg/dL, and stimulated serum cortisol concentration was less than 10 microg/dL. All clinical signs and symptoms and hypotension gradually improved after the oral prednisolone dose was increased to 10 mg/d. Clinicians must be aware of the possibility of CMV-induced adrenal insufficiency in renal transplant recipients. The condition may be symptomatic despite low-dose prednisolone therapy.

Objective: Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) infections in renal transplant recipients may cause significant morbidity and mortality. To manage these infections, established guidelines suggest that both the recipient and the donor be routinely tested for anti-CMV and anti-EBV antibodies prior to renal transplantation. The aim of this study was to assess the value of screening among people living in Iran., Patients and Methods: We retrospectively analyzed the incidences of CMV and EBV infections among 925 and 710 potential renal allograft donors and recipients, respectively, between 2005 and 2008. All cases were first transplantations. Enzyme-linked immunosorbent assays (ELISA) were performed to determine whether there were antibodies to CMV (IgG) or EBV viral capsid antigen (VCAIgG). Finally, we analyzed the seroprevalence and demographic factors., Results: Five hundred sixty-eight (61.40%) potential renal transplant donors and 483 (68.02%) potential renal transplant recipients were men. Donor ages ranged from 18 to 50 years (mean +/- SD, 34.7 +/- 8.1 years) and recipient ages ranged from 18 to 60 years (mean +/- SD, 45.9 +/- 7.3 years). Pretransplant CMV (IgG) and EBV (VCAIgG) seroprevalence was 100% among all donor, and recipient ages and sexes., Conclusion: Our findings suggested that kidney transplant centers in Iran do not need to perform routine screening for IgG antibodies to CMV and EBV among renal transplant recipients and donors of ages >or=18 years.

Our study sought to investigate the immune response of cytotoxic T lymphocytes to human cytomegalovirus (HCMV) in kidney transplant recipients with virus reactivation. Nine kidney transplant recipients with serum HCMV immunoglobulin G and HLA-A 0201 genotype displayed HCMV pp65 antigenemia and were compared with 29 control recipients who were free of antigenemia. The frequency of total HCMV-specific cytotoxic T cells was determined using HLA-A2-NLVPMVATV-pentamer staining. The frequency of HCMV specific interferon (INF)-gamma secreting CD8(+) T cells was determined using intracellular INF-gamma staining after NLVPMVATV pulsing in vitro. The proportion of IFN-gamma secreting pentamer-stained CD8(+) T cells was calculated, representing the capacity for INF-gamma secretion among HCMV-specific CD8(+) T cells. We observed that the frequency of HCMV-specific pentamer-stained CD8(+) T cells and HCMV-specific IFN-gamma secreting CD8(+) T cells both remained unchanged, yet the proportion of IFN-gamma secreting CD8(+) T cells showed a significant difference between the 2 groups (39.2% +/- 17.2% vs 20.0% +/- 13.3% respectively; P = .004), reflecting impaired IFN-gamma secreting capacity of HCMV-specific CD8(+) T cells among kidney transplant recipients displaying antigenemia, which may be a crucial reason for HCMV reactivation in immunosuppressed patients.

Objectives: Serological tests are essential for the donation process. We performed a study to identify the seroprevalence of cytomegalovirus (CMV), toxoplasmosis, HIV, Chagas disease, HTLV, hepatitis B virus (HBV), hepatitis C virus (HCV) and Lues among our potential donors., Methods: Among sera of 233 potential donors tested between January 2006 and April 2007, only 97 resulted in effective donation., Results: The seroprevalence of CMV immunoglobulin G (IgG) was 89.3%. Anti-HBc was positive in 63 samples (27%) and just three people were HBsAg antigen-positive. HIV, HCV, HTLV, and Chagas disease showed low prevalence among the potential donors. Toxoplasmosis IgG antibody had a high prevalence in the tested group., Conclusion: CMV and toxoplasmosis were prevalent in the whole sample.

To develop a rat model that allowed in vivo progressive human cytomegalovirus (HCMV) infection, allogeneic liver transplantation was performed across a rat combination of Dark Agouti (DA) to Brown Norway (BN). AD169, a well-characterized laboratory strain of HCMV, was used to establish a rat model of HCMV infection by injection of 0.4 mL (30.0 logTCID50) supernate into the rat peritoneum. Histological and blood specimens were obtained from animals sacrificed at predetermined timepoints. We performed immunohistochemical staining in liver, heart, kidney, spleen, and lung for HCMV immediate-early antigen (IE), lower matrix protein (pp65) detection in peripheral blood leukocytes, and HCMV early antigen (EA) and late antigen (LA). We compared survival rates. Our results showed positive HCMV IE and pp65 antigenemia detected in peripheral blood leukocytes in transplanted recipients from day 1 to day 30. Positive HCMV EA and LA staining cells were only detected in sections 10 days after liver transplantation, namely, in hepatocytes, mononuclear cells, bile duct epithelial cells, and endothelial cells. Successful HCMV replication was due to the combination of liver transplantation and cyclosporine (CsA) immunosuppression. Survival analysis showed no significant differences between the HCMV-infected group and HCMV-uninfected group. This new rat model of HCMV infection may be helpful to understand immune system modulation of HCMV infection.

Unlabelled: The usefulness of anti-CMV hyperimmune gammaglobulin (IgG-CMV, Cytotec) in lung transplant patients (LTx) is controversial. The objective of this study was to analyze the effectiveness of IgG-CMV in our LTx receptors., Patients and Methods: A retrospective study of LTx recipients treated with IgG-CMV as prophylaxis or as treatment for invasive disease. We used IgG-CMV associated with IV ganciclovir (GCV) as treatment for invasive disease. High-risk patients (CMV-negative recipients from CMV-positive donors; CMV-/+) were also with IgG-CMV prophylaxis during the first year. Other prophylactic uses of IgG-CMV were as an alternative to GCV in patients with related GCV toxicity, and as preemptive therapy in cases of persistent positive viral load (antigenemia > or = 1 cell and/or a PCR > or = 400) although oral GCV administration., Results: Between January 2000 and August 2003, 14 of the 74 lung transplant recipients (19%) received IgG-CMV as treatment for invasive disease (4 cases: 2 gastritis, 1 esophagitis, 1 hepatitis) and/or as prophylaxis (14 cases). All patients treated for invasive disease evolved favorably. No therapeutic failure were observed in CMV-/+ patients during treatment. Three of the six patients treated with IgG-CMV developed positive antigenemia despite treatment. The four patients treated for persistent antigenemia while receiving oral GCV achieved neutralization during the first month of treatment., Conclusion: IgG-CMV associated with Gancyclovir is effective as treatment for invasive disease and as pre-emptive therapy in patients with persistent positive viral load. In CMV-/+ recipients, IgG-CMV prevents pneumonitis and delays the development of invasive disease after the first year.

Antiviral antibodies clearly play a role in organ transplantation. The only antibody with a licensed indication for this population is CMVIG; however, the use of HBIG has become the standard of care for those patients at risk for HBV recurrence, and the use of VZIG would appear to be indicated for exposures to varicella-zoster in patients lacking immunity. Future studies defining the role of antiviral antibodies for therapy are necessary, and the role of antibody to prevent the EBV PTLD remains to be explored.

Our data suggest that CMVIG in combination with ganciclovir effectively reduces the incidence, and delays the onset of CMV infections in seropositive lung transplant recipients. In addition, its use may be associated with less severe CMV infection and a lower incidence of bacterial or fungal opportunistic infection. Although the number of patients in the study is small, high-titer CMVIG may be more effective than standard titer immunoglobulin in the prevention of CMV disease in lung transplant recipients. Several questions remain in addition to these: What is the optimal dosage and duration of treatment with CMVIG for prophylaxis of CMV infection and disease in lung transplant recipients; Is this strategy cost-effective; Will it reduce the incidence of obliterative bronchiolitis following lung transplantation and enhance allograft survival? A prospective, random-assignment trial is warranted to answer these questions.