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Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as well as kidney transplant patients with cytomegalovirus (CMV) and polyomavirus (BKV) infections. Using an antibody-based assay, we quantified ~ 350 cell surface markers, cytokines, and chemokines involved in inflammation and immunity. Unique protein signatures were identified specific to the acute phase of infection irrespective of the pathogen type, with significant changes during convalescence. In addition, tumor necrosis factor receptor superfamily member 6 (TNR6), C-C Motif Chemokine Receptor 7 (CCR7), and C-C motif chemokine ligand-1 (CCL1) were increased in the acute and convalescent phases across all viral, bacterial, and protozoan compared to blood from healthy donors. Furthermore, despite the differences between pathogens, proteins were enriched in common biological pathways such as cell surface receptor signaling pathway and response to external stimulus. In conclusion, we demonstrated that irrespective of the pathogen type, there are common immunoregulatory and proinflammatory signals.

BK virus (BKV) is a small DNA virus, a member of the polyomavirus family, that causes an opportunistic infection in immunocompromised patients, especially kidney transplant patients. This virus establishes a lifelong infection in most of the population, and once it reactivates in an immunocompromised state, leads to BKV nephropathy. This review seeks to assess the correlation between severe immunosuppression, evident by low CD4 cell counts in HIV-positive patients, and the reactivation of BKV, causing nephropathy. A literature review was conducted, extracting, and analyzing case reports of HIV-positive patients showing correlations between their degree of immunosuppression, as evidenced by their CD4 counts, and the degree of BKV infectivity, confirmed by kidney biopsy. A total of 12 cases of BKV nephropathy in HIV-infected patients were reviewed. A common finding was the presence of profound immunosuppression, with most patients having CD4 counts ≤50 cells/ mm3. A substantial number also had comorbid malignancies, with some undergoing chemotherapy, potentially increasing the risk of BKV reactivation. In addition to the HIV status and malignancies, other risk factors for BKV reactivation included older age, male gender, diabetes mellitus, Caucasian race, and ureteral stent placement. BKV nephropathy in HIV patients with native kidneys is closely correlated with severe immunosuppression. Although therapeutic strategies exist for post-transplant patients, aside from the treatment of HIV with highly active anti-retroviral therapy (HAART), which potentially helps with clearing BKV by increasing CD4 count, there is no definitive treatment for a native kidney BKV nephropathy in patients with AIDS. The complexity of the cases and severity of comorbidities indicate the need for further research to develop therapeutic strategies tailored to this population.

The article focuses on the evolution of lung transplantation as a standard treatment for life-threatening lung diseases and the challenges it still faces. Topics include the criteria for candidate selection and assessment, complications related to immunosuppression and infection risk post-transplant, and the ongoing need to address the gap between donor organ availability and growing demand.

Background Polyomavirus (PyV) nephropathy (PyVN) leads to kidney transplant dysfunction and loss. Since a definitive diagnosis requires an invasive kidney biopsy, a timely diagnosis is often hampered. In this clinical dilemma the PyV haufen-test, centering around the detection of 3-dimensional PyV aggregates in the urine, might provide crucial diagnostic information. Methods A multistep experimental design was used. The hypothesis was that PyV-haufen form within the kidneys under high concentrations of uromodulin, a kidney-specific protein and that PyV-haufen are, therefore, kidney-specific disease biomarkers. Results The first investigative step showed colocalization of uromodulin with aggregated PyV (1) in 10 kidneys with PyVN by immunohistochemistry, (2) in urine samples containing PyV-haufen by electron microscopy/immunogold labeling (n = 3), and (3) in urine samples containing PyV-haufen by immunoprecipitation assays (n = 4). In the in vitro experiments of the next step, only high uromodulin concentrations (≥1.25 mg/mL) aggregated PyV, as is expected to occur within injured nephrons. In contrast, in voided urine samples (n = 59) uromodulin concentrations were below aggregation concentrations (1.2−19.6 µg/mL). In the third investigative step, none of 11 uromodulin−/− knockout mice (0%) with histologic signs of PyVN showed urinary PyV-haufen shedding, compared with 10 of 14 uromodulin+/+ wild-type mice (71%). Conclusions PyV-haufen form within kidneys under high uromodulin concentrations. Thus, PyV-haufen detected in the urine are specific biomarkers for intrarenal disease (ie, definitive PyVN). [ABSTRACT FROM AUTHOR]

Background: Currently, few literature reports document cases of decoy cells in the urine of umbilical cord blood transplant patients. The majority of the literature indicates that decoy cells are frequently identified in the urine of kidney transplant recipients. Case presentation: This case report describes a patient with Myelodysplastic Neoplasms featuring a complex karyotype who underwent umbilical cord blood transplantation. Postoperative urinary cytology revealed decoy cells, and subsequent BK virus nucleic acid testing was positive. However, the routine use of antiviral drugs by the physicians led to insufficient attention to the decoy cells and BK virus, culminating in hemorrhagic cystitis. Conclusions: Urine cytology is a simple, intuitive, rapid, and cost-effective analytical method. The presence of decoy cells in the urine can serve as an indicator for infection screening and provide a clue for clinical doctors: Detection of decoy cells in urine should prompt a more vigorous antiviral response to mitigate the risk of complications like hemorrhagic cystitis. [ABSTRACT FROM AUTHOR]

Background: Long‐term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single‐stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status. Aims: TTV‐based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long‐term patient and graft survival. Methods: Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library. Results: The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High‐TTV load and high immunosuppression are associated with a risk of infection, and low‐TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner et al. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections. Conclusion: Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV‐guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation. [ABSTRACT FROM AUTHOR]

BK virus (BKV) encephalitis is a rare complication after hematopoietic stem cell transplantation (HSCT). A 43-year-old woman with recurrent follicular lymphoma after autologous HSCT received allogeneic bone marrow transplantation from a human leukocyte antigen-matched related donor. Neutrophil engraftment was achieved on post-transplant day 13. Memory loss and noncooperative attitude toward the medical staff were observed on day 16, and her mental status worsened progressively. Magnetic resonance imaging (MRI) showed nonspecific findings on day 19; however, cerebrospinal fluid (CSF) analysis including real-time polymerase chain reaction on day 20 revealed elevated levels of BKV 4.67 × 104 copy/mL. BKV encephalitis was diagnosed based on CSF findings, intravenous administration of immunoglobulin and cidofovir was started, and the immunosuppressive agent dose was reduced. Diffusion-weighted MRI on day 28 showed signal abnormalities in the bilateral periventricular white matter. Although the follow-up CSF analysis on day 35 was negative for BKV, her mental status and MRI findings did not improve, and she died on day 55 because of respiratory failure. This case emphasizes the importance of considering BKV encephalitis as a differential diagnosis of post-transplant encephalitis, considering the central nervous system-associated immune reconstitution inflammatory syndrome in patients with worsening central nervous system findings after eradication of BKV in the CSF. [ABSTRACT FROM AUTHOR]

Background: BK-polyomavirus (BKpyV) nephropathy (BKVN) is associated with end-stage kidney disease in kidney and non-kidney solid organ transplantation, with no curative treatment. Case presentation: A 45-year-old woman with a past medical history of double lung transplantation subsequently developed end-stage kidney disease, of undetermined origin. One month after receiving a kidney transplant, a diagnosis of early BKVN was suspected, and in retrospect was a reasonable cause for the loss of her native kidneys. Minimisation of immunosuppression, achieved through extracorporeal photopheresis, allowed clearance of BKpyV and so prevented nephropathy. Both lung and kidney grafts had a satisfactory and stable function after one year of follow-up, with no rejection. Conclusions: Extracorporeal photopheresis may have facilitated minimisation of immunosuppression and BKpyV clearance without lung allograft rejection. [ABSTRACT FROM AUTHOR]

Background: Human Immunodeficiency Virus (HIV) and malaria are two major diseases in sub-Saharan Africa. Co-infection can significantly impact the clinical outcomes of both conditions. We assessed the proportion of HIV-infected children at Korle Bu Teaching Hospital (KBTH) and Princess Marie Louise Hospital (PML) with malaria parasites. The association between asymptomatic malaria parasitaemia and virological non-suppression was also determined in these children. Methods: This cross-sectional study of 277 asymptomatic malaria in children receiving care at paediatric HIV clinics at KBTH and PML was conducted from September to November 2022. Patients who had been on antiretroviral therapy (ART) for at least six months were eligible to participate. Structured questionnaires were used to collect socio-demographic information, malaria prevention behaviors, and ART-related data using in-person interviews. Microscopy and PCR were used to screen for malaria, and GeneXpert was used to determine viral load. To examine the determinants of malaria PCR positivity and virological non-suppression, chi-square tests and logistic regression were performed. Results: The median age of the participants was 9 years (range: 6–12 years). Males comprised 158 (57%) of the study population. We detected 10 (3.6%) and 21 (7.6%) malaria cases by microscopy and PCR, respectively. Virological non-suppression (VL > 1000 copies/ml) was observed in 82 (29.6%) of the 277 participants. Among the suppressed individuals, 62 (22.4%) exhibited low-level viraemia (VL level 40-1000 copies/ml) and 133 (48%) had undetectable viral load levels. No factors were associated with the presence of malaria PCR positivity carriage. Poor adherence to ART was associated with a five-fold increase in the risk of viral load non-suppression (AOR = 4.89 [CI = 2.00-11.98], p = 0.001). Conclusion: The proportion of children living with HIV with asymptomatic malaria parasitaemia was low. Approximately one-third of the study population had virological non-suppression. The interaction between malaria parasitemia and viral replication may not be the main cause for virological non-suppression in this low transmission area. [ABSTRACT FROM AUTHOR]

BK polyomavirus infection is an important cause of graft loss in transplant patients, however, currently available therapies lack effectiveness against this pathogen. Identification of immunological targets for potential treatments is therefore necessary. The aim of this study was to predict candidates of immunodominant epitopes within four BK virus proteins (VP1, VP2, VP3 and LTA) using PBMCs from 44 healthy donors. We used the ELISpot epitope mapping method to evaluate the T‐cell response, and HLA‐peptide binding was predicted using the NetMHCpan algorithm. A total of 11 potential peptides were selected for VP1, 3 for VP2/VP3 and 13 for LTA. Greater reactivity was observed for VP1 and LTA proteins compared with VP2/VP3. Most of the peptides selected as potential immunodominant candidates were restricted towards several HLA class I and II alleles, with predominant HLA class I binding by computational predictions. Based on these findings, the sequences of the selected immunodominant epitopes candidates and their corresponding HLA restrictions could contribute to the optimisation of functional assays and aid in the design and improvement of immunotherapy strategies against BK virus infections. [ABSTRACT FROM AUTHOR]

Background: In kidney transplantation, concerns have been raised regarding increased incidence of viral opportunistic infections in hepatitis C virus (HCV) nucleic acid test (NAT)‐negative (‐) recipients who received HCV NAT‐positive (+) donor kidneys, specifically BK polyomavirus (BKPyV), cytomegalovirus (CMV), and Epstein‐Barr virus (EBV). The purpose of this study was to determine the incidence of these three viral opportunistic infections in HCV NAT‐ recipients who have undergone kidney transplantation with HCV NAT+ donor kidneys at our institution. Methods: This was an Institutional Review Board‐approved, single‐center, retrospective case‐control study of HCV NAT‐ kidney transplant recipients with HCV NAT+ donors from 2018 to 2021. The primary outcome was the cumulative incidence of viral infections of BKPyV, CMV, and/or EBV within 1 year following kidney transplantation. Results: A total of 231 patients were included, 77 in the exposed (donor HCV NAT+) group and 154 in the control (donor HCV NAT‐) group. The adjusted cumulative incidence of viremia within 1 year did not statistically differ between groups (77% exposed group versus 66% for the control group, hazard ratio 1.34, 95% confidence interval 0.95–1.89). In addition, no statistically significant differences were observed for secondary outcomes with the exception of CMV viremia (62% exposed versus 49% control, p = 0.021). However, there were more patients in the exposed group at high risk for CMV viremia based on serostatus (CMV Donor+/Recipient‐, D+/R‐). Conclusion: Among patients who received HCV NAT+ donor kidneys, no clear association was observed between exposure to HCV NAT+ donor kidneys and viral infections of BKPyV, CMV, or EBV. [ABSTRACT FROM AUTHOR]

Aims: This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. Methods: In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. Findings: HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. Conclusion: Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions BK polyomavirus‐associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV).We report the results of a phase I/II, double‐blind, placebo‐controlled randomized dose‐escalation trial of cidofovir in KTRs with biopsy‐confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min. Intravenous cidofovir (0.25 mg/kg/dose or 0.5 mg/kg/dose) or placebo was administered on days 0, 7, 21, and 35, with final follow‐up through day 49.The trial was prematurely discontinued due to slow accrual after 22 KTRs had completed the study. Cidofovir was safe and tolerated at the doses and duration studied. The proportion of subjects with any adverse event (AE) was similar between groups (9/14 [64%] in the combined cidofovir dose groups and 6/8 [75%] in the placebo group); 84% of AEs were mild. BKPyV DNAemia reduction by day 49 was similar between groups (>1 log10 reduction in (2/9 [22.2%] of 0.25 mg/kg group, 1/5 [20%] of 0.5 mg/kg group, and 2/8 [25%] of placebo group).These preliminary results indicate that low‐dose cidofovir was safe and tolerated but had no significant BKPyV‐specific antiviral effect in KTRs with BKPyVAN. [ABSTRACT FROM AUTHOR]

Posttransplantation complications pose a major challenge to the long‐term survival and quality of life of organ transplant recipients. These complications encompass immune‐mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft‐versus‐host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients. [ABSTRACT FROM AUTHOR]

Abstract Background Currently, few literature reports document cases of decoy cells in the urine of umbilical cord blood transplant patients. The majority of the literature indicates that decoy cells are frequently identified in the urine of kidney transplant recipients. Case presentation This case report describes a patient with Myelodysplastic Neoplasms featuring a complex karyotype who underwent umbilical cord blood transplantation. Postoperative urinary cytology revealed decoy cells, and subsequent BK virus nucleic acid testing was positive. However, the routine use of antiviral drugs by the physicians led to insufficient attention to the decoy cells and BK virus, culminating in hemorrhagic cystitis. Conclusions Urine cytology is a simple, intuitive, rapid, and cost-effective analytical method. The presence of decoy cells in the urine can serve as an indicator for infection screening and provide a clue for clinical doctors: Detection of decoy cells in urine should prompt a more vigorous antiviral response to mitigate the risk of complications like hemorrhagic cystitis.

Background: BK virus (BKV) is a member of the polyomavirus family. The determination of anti-BKV immunoglobulin G (IgG) antibody levels in kidney donors and recipients has been reported as a possible predictor of the risk of BK nephropathy. Allograft dysfunction is a significant risk factor. The main objective of this study was to address the high prevalence of renal failure due to BKV nephropathy in kidney transplant recipients. This investigation aims to determine whether donors and recipients of renal transplants had BKV IgG antibodies before transplantation. Methods: Blood samples were collected from 46 kidney transplant recipients and their corresponding 46 donors. An enzyme-linked immunosorbent assay was used to qualitatively analyze human BKV IgG. Results: Ninety-two participants, 46 kidney transplant donors, and 46 kidney transplant recipients, were analyzed. Pretransplantation anti-BKV antibody levels were higher in kidney transplant donors (73%) than in recipients (63%). Donors and recipients included in the study were grouped into seropositive and seronegative recipients, with the highest proportion of seropositive recipient-donor groups (48%) and the lowest percentages in the seronegative donor and seronegative recipient groups. Fifty-one percent of the participants were male and 49% were female. The age distribution of most subjects was >50 years old. Conclusion: BKV can cause kidney transplant rejection. Routine screening of transplant recipients and donors for BKV IgG seropositivity is recommended before renal transplantation. This can improve transplant outcomes and prevent rejection.

Abstract Aims This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. Methods In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. Findings HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. Conclusion Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies.

The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman's correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233. [ABSTRACT FROM AUTHOR]

This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN). First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3–5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy. We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9–17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer. Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight. [ABSTRACT FROM AUTHOR]

This retrospective study aims to investigate the prevalence and immunopathologic characteristics of seropositive and seronegative hepatitis B virus-associated membranous nephropathy (HBV-MN). Clinicopathologic and serologic records of 420 patients with histologically confirmed HBV-MN between January 2014 and July 2021 were examined to determine the prevalence of seropositive and seronegative HBV-MN. Serum anti-PLA2R antibody testing was conducted on 280 patients with HBV-associated membranous nephropathy (HBV-MN) from August 2018 to July 2021. Immunopathologic characteristics of HBV-MN patients and anti-PLA2R antibody positivity were analyzed. Among 420 pathologically confirmed HBV-MN patients, 230 (54.8%) were seropositive for HBV. The seropositive group exhibited higher blood creatinine values and incidence of liver function abnormalities than the seronegative group (p <.05). Serum anti-PLA2R antibody testing on 280 HBV-MN patients revealed a total positive rate of 44.6%, with the seronegative group showing a significantly higher rate (62.6%) compared to the seropositive group (32.1%) (p <.01). The anti-PLA2R antibody-positive group displayed higher levels of urine protein (p <.05), serum cholesterol (p <.01), and IgG4 subtypes (p <.05) compared to the negative group. Additionally, the positive group had significantly lower levels of serum albumin and IgG than the negative group (p <.01). This comprehensive study reveals a significantly higher prevalence of seronegative HBV-MN than previously thought. The blood creatinine values and incidence of liver function abnormalities was higher in the serology-positive group than in the serology-negative group. Notably, the seronegative group displayed a higher positive rate of anti-PLA2R antibodies compared to the seropositive group, indicating distinctive clinical and immunopathologic features. [ABSTRACT FROM AUTHOR]

Introduction: JC-polyomavirus-associated nephropathy (JC-PVAN) is a rare cause of allograft dysfunction with only a few cases described in the literature. Case Presentation: We present 2 cases of JC-PVAN, both of which occurred >5 years after kidney transplantation. In both cases, transplant biopsies were performed because of worsening of kidney function. We found tubulitis and interstitial inflammation; immunohistochemistry was positive for SV40, but BK virus was not detected. The presence of JC virus confirmed the diagnosis of JC-PVAN. Immunosuppressive therapy was adopted, but in both cases graft function progressively deteriorated. Conclusions: Our cases show that JC-PVAN, although much rarer than BK-PVAN, should be considered a possible cause of graft dysfunction even years after transplantation. Complete diagnostic workup, including kidney biopsy, is crucial for correct diagnosis and treatment.

Polyomaviruses, particularly BK virus, are ubiquitous latent infections that may reactivate with immunosuppression during kidney transplantation, resulting in polyomavirus nephropathy (PVN). The levels of viruria and viremia serve as tools for screening and making a presumptive diagnosis of PVN, respectively, while a definitive diagnosis requires a kidney biopsy. There are histologic classifications of PVN based on the extent of tubular cell viral infection, interstitial fibrosis, and interstitial inflammation. These classifications correlate to some degree with graft function and loss, aiding in determining treatment efficacy and prognostication. PVN has histologic overlap with acute cell-mediated rejection, making the differential diagnosis challenging, although there are suggestive features for these different causes of graft dysfunction. This article reviews the diagnosis, histologic findings, and classifications of PVN, and discusses how to differentiate viral nephropathy from acute rejection.

Introduction: JC-polyomavirus-associated nephropathy (JC-PVAN) is a rare cause of allograft dysfunction with only a few cases described in the literature. Case Presentation: We present 2 cases of JC-PVAN, both of which occurred >5 years after kidney transplantation. In both cases, transplant biopsies were performed because of worsening of kidney function. We found tubulitis and interstitial inflammation; immunohistochemistry was positive for SV40, but BK virus was not detected. The presence of JC virus confirmed the diagnosis of JC-PVAN. Immunosuppressive therapy was adopted, but in both cases graft function progressively deteriorated. Conclusions: Our cases show that JC-PVAN, although much rarer than BK-PVAN, should be considered a possible cause of graft dysfunction even years after transplantation. Complete diagnostic workup, including kidney biopsy, is crucial for correct diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Despite the high prevalence of BK polyomavirus (BKPyV) and the associated risk for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant (KTX) recipients, many details on viral processes such as replication, maturation, assembly and virion release from host cells have not been fully elucidated. VP1 is a polyomavirus-specific protein that is expressed in the late phase of its replicative cycle with important functions in virion assembly and infectious particle release. This study investigated the localization and time-dependent changes in the distribution of VP1-positive viral particles and their association within the spectrum of differing cell morphologies that are observed in the urine of KTX patients upon active BKPyV infection. We found highly differing recognition patterns of two anti-VP1 antibodies with respect to intracellular and extracellular VP1 localization, pointing towards independent binding sites that were seemingly associated with differing stages of virion maturation. Cells originating from single clones were stably cultured out of the urine sediment of KTX recipients with suspected BKPyVAN. The cell morphology, polyploidy, virus replication and protein production were investigated by confocal microscopy using both a monoclonal (mAb 4942) and a polyclonal rabbit anti-VP1-specific antibody (RantiVP1 Ab). Immunoblotting was performed to investigate changes in the VP1 protein. Both antibodies visualized VP1 and the mAb 4942 recognized VP1 in cytoplasmic vesicles exhibiting idiomorphic sizes when released from the cells. In contrast, the polyclonal antibody detected VP1 within the nucleus and in cytoplasm in colocalization with the endoplasmic reticulum marker CNX. At the nuclear rim, VP1 was recognized by both antibodies. Immunoblotting revealed two smaller versions of VP1 in urinary decoy cell extracts, potentially from different translation start sites as evaluated by in silico analysis. Oxford Nanopore sequencing showed integration of BKPyV DNA in chromosomes 3, 4 and 7 in one of the five tested primary cell lines which produced high viral copies throughout four passages before transcending into senescence. The different staining with two VP1-specific antibodies emphasizes the modification of VP1 during the process of virus maturation and cellular exit. The integration of BKPyV into the human genome leads to high virus production; however, this alone does not transform the cell line into a permanently cycling and indefinitely replicating one. [ABSTRACT FROM AUTHOR]

A recent study published in Transplant International explores the use of stem cell-derived islet transplantation as a potential treatment for type 2 diabetes. The study details the successful transplantation of islet tissue derived from induced pluripotent stem cells into a patient with type 2 diabetes, which resulted in improved islet function. However, the study also acknowledges the need for more information on quality control and the limitations of diagnosing the patient's diabetes. The authors suggest that further research is necessary to fully understand the safety and effectiveness of this treatment. The document provides a summary of the study, including information on its focus, findings, and the authors' contributions and funding. [Extracted from the article]

Background: Epstein–Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV‐driven malignancies. The most frequent EBV‐induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV‐associated smooth muscle tumors (EBV‐SMT). EBV‐SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV‐SMT (PT‐SMT) are scarce in kidney transplant recipients. Methods: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT‐SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT‐SMT, evolution of graft function, and patient survival. Results: Eight patients were included. The median age at PT‐SMT diagnosis was 31 years (range 6.5–40). PT‐SMT occurred after a median delay of 37.8 months after transplantation (range 6–175). PT‐SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow‐up after PT‐SMT diagnosis (median 33 months (range 17–132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow‐up. Conclusion: PT‐SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT‐SMT is low in kidney transplant recipients (0.07% in our cohort), PT‐SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients. [ABSTRACT FROM AUTHOR]

Background: Norovirus is the most common cause of viral gastroenteritis. Studies in adult kidney recipients have documented significant morbidity associated with norovirus infection, but there are few studies in pediatric recipients. Methods: Multicenter retrospective cohort study of pediatric kidney transplant recipients with norovirus, confirmed by stool PCR, between January 1, 2008, and December 31, 2018. Outcomes of interest included duration of diarrhea, incidence of chronic diarrhea, management strategies, and graft function. Results: Forty pediatric kidney transplant recipients from four centers were identified for inclusion. Median age at transplant was 5.4 years (IQR 2.2–11.2 years), and median time post‐transplant was 1.9 years (IQR 0.8–3.8 years). Median diarrheal duration was 16 days (IQR 6.0–41.5 days); 15 patients (43%) had acute diarrhea, 8 (23%) had persistent, and 12 (30%) had chronic diarrhea. Twenty‐one (53%) patients developed acute kidney injury. Thirty‐five (88%) patients required supplemental fluids, 8 (20%) patients underwent immunosuppression reduction for a median of 22 days, 5 (13%) were treated with nitazoxanide, and 5 (13%) received oral immunoglobulin. Acute rejection was diagnosed in 3 (8%) patients within 6 months of norovirus diagnosis. We observed no sustained decline in eGFR at 12 months after diarrhea resolution (median eGFR difference: 2.8 mL/min/1.73 m2 [IQR: −17.1, 7.4]). Of the patients in the cohort, two lost their graft at 6.8 and 30.0 months after the onset of diarrhea. Conclusion: Norovirus is associated with significant morbidity in pediatric kidney transplant recipients. Various treatment interventions are being employed for norovirus infection. Larger studies, both observational and interventional, are needed to determine the optimal treatment. [ABSTRACT FROM AUTHOR]

Background: Antibody‐mediated rejection is one of the most significant risk factors for allograft dysfunction and failure in children and adolescents with kidney transplants, yet optimal treatment remains unidentified. To date, there are mixed findings regarding the use of Bortezomib, a plasma cell apoptosis inducer, as an adjunct therapy in the treatment of antibody‐mediated rejection. Methods: In a retrospective single center study, we reviewed the efficacy and tolerability of bortezomib as adjunct therapy for treatment‐refractory antibody‐mediated rejection. Results: Six patients with a median age of 14.6 years (range 6.9–20.1 years) received bortezomib at a mean of 71 months (range 15–83 months) post‐kidney transplant. Four patients experienced decline in estimated glomerular filtration rate (eGFR) from 4% to 42%. One patient started bortezomib while on hemodialysis and did not recover graft function, and another patient progressed to hemodialysis 6 months after receiving bortezomib. Although DSA did not completely resolve, there was a statistically significant decline in DSA MFI pre and 12‐months post‐BZ (p =.012, paired t‐test) for the subjects who were not on dialysis at the time of bortezomib. Chronic Allograft Damage Index (CADI) score of ≥3 was seen in all six subjects at their biopsy prior to therapy. No adverse effects were reported. Conclusions: Bortezomib was well tolerated and resulted in improvements in MFI of DSA among four pediatric subjects without allograft failure, although no effects were observed on eGFR trajectory. Further studies are needed to clarify whether earlier intervention with bortezomib could prevent renal failure progression. [ABSTRACT FROM AUTHOR]

Background: BK polyomavirus (BKV) DNAemia is a challenging infectious complication after kidney transplant (KT). Reduction of immunosuppression is the mainstay of management, and tacrolimus is often the first immunosuppressive medication adjusted upon the diagnosis of BKV DNAemia. This study aimed to evaluate the impact of a new institutional protocol with lower target tacrolimus levels on BKV DNAemia, allograft rejection, and de novo donor‐specific antibodies (dnDSA) among pediatric KT recipients. Methods: We conducted a retrospective chart review of all KT episodes between January 2013 and December 2018. The new protocol with lower target tacrolimus levels was implemented in March 2015. One hundred twenty‐seven patients were included in primary analysis. All patients received induction with basiliximab and methylprednisolone and were maintained on a steroid‐based immunosuppressive regimen. Results: In the post‐intervention cohort, cumulative incidence of BKV DNAemia at 100 days (13.4% vs. 17.8%, p =.605) and 18 months post‐KT (34.1% vs. 26.7%, p =.504) was not significantly different from the pre‐intervention cohort. Biopsy‐proven rejection rate did not change. However, we observed a trend toward earlier development of dnDSA in the post‐intervention cohort using the Kaplan–Meier survival analysis (log‐rank p =.06). Younger recipient age at the time of transplant was found to slightly increase the risk of BKV DNAemia (OR: 1.09, 95% CI [1.01, 1.16], p =.024). There was an association between BKV DNAemia and biopsy‐proven rejection of any type (adjustedOR: 2.77, 95% CI [1.26, 6.23], p =.012), especially acute T‐cell‐mediated rejection grade 1A and above (adjustedOR: 2.95, 95% CI [1.06, 8.30], p =.037), after adjusted for recipient age at the time of transplant. Conclusions: Targeting lower tacrolimus levels did not decrease the incidence of BKV DNAemia within 100 days or 18 months post‐KT, nor did it increase the risk of biopsy‐proven rejection among pediatric KT recipients in our center. However, there was a trend toward earlier development of dnDSA, which may portend worse long‐term graft outcome post‐KT. Our findings highlight the need for individualized immunosuppressive regimens based on immunologic and infectious risk factors and the importance of implementing innovative biomarkers to guide therapy and improve outcomes. [ABSTRACT FROM AUTHOR]

This article examines the effectiveness of monoclonal antibodies (mAbs) in neutralizing SARS-CoV-2 variants in kidney transplant recipients. The study found that certain mAbs had low levels of neutralizing activity against specific variants, but in vivo neutralization showed slightly increased activity after administration. The article suggests that even though these variants are no longer circulating, there is still residual antiviral activity. The study also discusses the potential benefits of increasing the dosage of mAbs to enhance their efficacy against COVID-19 variants. However, the study has limitations, and further research is needed to better understand antibody activity and optimize patient care. Funding for the research was received from various sources, and some authors have declared potential conflicts of interest. [Extracted from the article]

Objective: To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). Methods: A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. Results: The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p < 0.05). Compared to the control group, the HCQ treatment group had fewer patients who were converted from low risk to moderate-to-high risk (p = 0.084). There were also no severe adverse reactions in the HCQ treatment group. Conclusion: In patients with low risk PLA2R-associated MN, adequate supportive therapy combined with HCQ is superior to supportive therapy alone in controlling proteinuria and reducing serum PLA2R antibody titers. Additionally, our study demonstrated that the incidence of adverse reactions did not increase. Trial registration: This study was registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR1900021757, Date of registration: 2019-03-08). [ABSTRACT FROM AUTHOR]

Infection management in solid organ transplantation poses unique challenges, with a diverse array of potential pathogens and associated antimicrobial therapies. With limited high-quality randomized clinical trials to direct optimal care, therapeutic "myths" may propagate and contribute to suboptimal or excessive antimicrobial use. We discuss 6 therapeutic myths with particular relevance to solid organ transplantation and provide recommendations for infectious diseases clinicians involved in the care of this high-risk population. [ABSTRACT FROM AUTHOR]

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. Methods: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. Results: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133–595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. Conclusion: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature review aimed to identify sequelae in adults within 1 year following RSV-related hospitalization or resolution of acute infection. Methods: Studies were identified from Embase, MEDLINE, LILACS, SciELO, and grey literature. Random-effects meta-analyses using restricted maximum likelihood were used to calculate the proportions and relative risks of sequelae in patients with RSV compared with controls (patients with RSV-negative influenza-like illness, influenza, and parainfluenza) per follow-up period, population, and treatment setting, where possible. Results: Twenty-one relevant studies covering the period from 1990 to 2019 were included. Among the general population, the most frequent clinical sequela was sustained function loss (33.5% [95% CI 27.6–39.9]). Decline in lung function and cardiovascular event or congestive heart failure were also identified. Utilization sequelae were readmission (highest at > 6 months after discharge) and placement in a skilled nursing facility. The only subpopulation with data regarding sequelae was transplant patients. Among lung transplant patients, the most frequently reported clinical sequelae were decline in lung function, followed by graft dysfunction and bronchiolitis obliterans syndrome. Pooled relative risks were calculated for the following sequela with controls (primarily influenza-positive patients): cardiovascular event (general population) and pulmonary impairment (hematogenic-transplant patients) both 1.4 (95% CI 1.0–2.0) and for readmission (general population) 1.2 (95% CI 1.1–1.3). Conclusions: Although less data are available for RSV than for influenza or other lower respiratory tract infections, RSV infection among adults is associated with medically important sequelae, with a prevalence similar to other respiratory pathogens. RSV sequelae should be included in disease burden estimates. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients require potent immunosuppression and are predisposed to opportunistic infections, many of which have a viral etiology. Currently, viral assays detect and quantify single pathogens using PCR or qPCR. An unbiased sequencing method with comparable accuracy would allow simultaneous monitoring of multiple viral pathogens and nonpathogenic Anelloviridae. The quantification of donor-derived cell-free DNA (dd-cfDNA) is an established method for the detection of allograft rejection, and a single workflow combining dd-cfDNA quantification and viral detection represents an opportunity to improve patient monitoring and management. Whole genome sequencing of cell-free DNA was performed using 1,980 plasma samples from 256 subjects enrolled in a multi-center study. Non-human sequences underwent reference-assisted assembly and taxonomic annotation of the viral DNA pathogens. Of the 1,980 samples tested, 1,453 (73.4%) had ≥1 viral detection(s), either a known viral pathogen or torque teno virus (TTV), with positivity rates generally declining 12–18 months post-transplant. Concordance of metagenomic NGS (mNGS) viral detection with qPCR detection was 97.7% (94.1% sensitivity, 98.2% specificity), and a linear relationship was demonstrated between mNGS viral quantitation and qPCR results. BK virus, cytomegalovirus, and Epstein-Barr virus were detected by sequencing up to 60 days prior to independently established clinical diagnoses. Whole-genome sequencing allows simultaneous quantification of dd-cfDNA as well as sensitive and early detection of viral infection through secondary analysis of the same sequencing results. In combination with dd-cfDNA, mNGS viral detection may provide additional pathogen surveillance results and serve as a useful biomarker for both over- and under-immunosuppression. [ABSTRACT FROM AUTHOR]

BK virus nephropathy (BKVN) is a significant complication in kidney transplant recipients, resulting in graft dysfunction and potentially leading to graft loss. This study aims to investigate the incidence and outcomes of BKVN in kidney transplant recipients receiving steroid-free maintenance immunosuppression in a Latin -American cohort. Case series study of BKVN among kidney transplant recipients who underwent transplantation between 2008 and 2023. The primary outcome was graft loss caused by BKVN, excluding death with function. Secondary outcomes included graft function and acute rejection episodes. The statistical analysis involved descriptive statistics and the Kaplan-Meier (K-M) method to plot the overall probabilities of not initiating dialysis. During the 15-year period, 2236 kidney transplants were performed, BKVN was histologically diagnosed in 38 kidney recipients and 33 cases were analyzed. Median age was 50 years and men were 48.5% of patients. A total of 45.4% of BKVN occurred within the first 12 months of transplant. The incidence of BKVN was 1.6% but it varied by era. The rate of graft loss was 75.7% (25 cases). The K-M graft survival probability at 6 months and 12 months after diagnosis of BKVN was 38.3% (95% CI 24.7–59.4) and 22.3% (95% CI 11.7–42.8), respectively. BKVN affected 1.6% of transplant recipients and it was associated with high-rate of graft loss. We observed that significant graft disfunction at the time of diagnosis resulted in worse outcomes with a reduced probability of graft survival. [ABSTRACT FROM AUTHOR]

Polyomaviruses BK (BKPyV) and JC (JCPyV), belonging to the Polyomaviridae, are responsible for human pathologies. In kidney transplant recipients, BKPyV replication can lead to irreversible nephron damage whereas JCPyV replication remains asymptomatic. Concomitant replication is rare and potential competition between the infections has been described. The aim of this retrospective case‐control study was to describe the molecular epidemiology and risk factors associated with BKPyV and JCPyV replication in a cohort of kidney transplant recipients. In total, 655 urine samples from 460 patients were tested for BKPyV and JCPyV DNA. Positive samples were submitted to strain genotyping. Demographic and clinical characteristics were also compared. Isolated JCPyV and BKPyV was found in 16.5% and 23.3% of patients, respectively; co‐replication was rare (3.9%). BKPyV strains Ib‐2, Ib‐1, and IVc‐2 were the most prevalent. JCPyV strains mostly belonged to genotypes 4 and 1B. During follow‐up, JCPyV shedding significantly reduced the risk of BKPyV DNAuria, with an odds ratio of 0.57 (95% confidence interval: 0.35–0.99), and was associated with better prognosis than BKPyV replication, based on the estimated glomerular filtration rate. Molecular epidemiology of BKPyV and JCPyV strains in our region was similar to previous studies. This study suggests that JCPyV is benign and appears to limit damaging BKPyV replication. JCPyV DNAuria screening could thus be a useful strategy to predict BKPyV‐related outcomes. [ABSTRACT FROM AUTHOR]

The most prevalent malignancy that complicates both adult and pediatric solid organ transplantation is post‐transplant lymphoproliferative disorder (PTLD). This study aimed to analyze the clinical and pathological characteristics, treatments, and outcomes of Epstein‐Barr virus (EBV) DNAemia and PTLD in pediatric liver transplant recipients. A retrospective chart review was performed on 112 patients less than 18 years of age who underwent isolated orthotopic liver transplantation (OLT) between 2010 and 2022 at Ege University Children's Hospital. Data gathered for 1‐year post‐OLT included age at OLT, EBV, immunoglobulin (Ig)M/IgG status of the donor and recipient, indication for OLT, induction regimen, all immunosuppression levels, date and result of EBV polymerase chain reaction testing, rejection episodes documented by liver biopsy, and the development of PTLD. Forty‐nine patients (43.75%) developed EBV DNAemia (median interval from surgery: 2 months, min–max: 2–36), of which 43 (87.8%) grafts came from living donors, and 6 (12.2%) came from deceased donors. Nine (18.4%) patients died during follow‐up, and eight (16.3%) developed PTLD. Of these 8 patients; five patients developed EBV‐related disease, one child developed hemophagocytic lymphohistiocytosis, one developed aplastic anemia, and one child developed B cell lymphoma. When PTLD patients and without‐PTLD patients were compared, pediatric intensive care unit hospitalization, abnormal bone marrow biopsy findings, lymphadenopathy, age at diagnosis of EBV DNAemia, EBV viral load, tacrolimus (FK 506) pre‐infection, were higher and tacrolimus 1‐month levels were lower in patients with PTLD (p < 0.05). In logistic regression analysis, we showed that the age at diagnosis of EBV DNAemia was significantly higher in children with PTLD (p = 0.045; OR: 1.389; 95% CI: 1.007–1.914). PTLD is a rare but severe complication associated with EBV after OLT. This study demonstrated that PTLD is associated with older age, higher tacrolimus blood levels before EBV DNAemia, and higher peak EBV viral load at 1 month of EBV DNAemia. [ABSTRACT FROM AUTHOR]

Background: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. Purpose: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). Study Type: Prospective. Subjects: Seventy‐seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well‐functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). Field Strength/Sequence: 1.5 T/T2‐weighted imaging and DTI. Assessment: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. Statistical Test: One‐way analysis of variance; correlation analysis; independent‐sample t‐test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P‐value <0.05. Results: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 μmol/L vs. 82.3 ± 20.9 μmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. Data Conclusion: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. Evidence Level: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

The article "A Hitchhiker's Guide to the BK Galaxy" published in Transplant International discusses the challenges posed by the BK polyomavirus in kidney transplant patients. It highlights the importance of following the Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation. The article suggests a lean approach to implementing the guidelines, focusing on an infographic, conceptual timeline, and flowchart for clinical translation. It emphasizes the need for a multidisciplinary team approach to harmonize and successfully implement the guidelines, with a focus on reducing immunosuppression guided by plasma BK polyomavirus DNA load. The article also identifies areas of uncertainty and the need for further research to improve outcomes for kidney transplant recipients. [Extracted from the article]

The article "Transplant Trial Watch" discusses a study on heart transplant recipients comparing outcomes of everolimus versus a standard regimen. The study followed participants for 12 years and found a significant benefit in renal function for the everolimus group. Another study in the article focuses on a novel monoclonal antibody, MAU868, targeting BK polyomavirus VP1, showing promising results in safety and tolerability. These studies offer potential advancements in heart transplantation and BK virus treatment, respectively. [Extracted from the article]

The article "Current Challenges and Advances on Infectious Diseases in Solid Organ Transplantation" discusses the impact of infections on solid-organ transplant recipients, highlighting the role of immunosuppressive drugs and surgical procedures in shaping infection epidemiology. Various topics such as managing infections, antibiotic approaches, and innovative strategies like fecal transplantation are covered. The article also delves into specific infections like cytomegalovirus and multidrug-resistant organisms, emphasizing the need for advanced diagnostics and access to new antibiotics to improve outcomes in transplant recipients. Overall, the article provides a comprehensive overview of transplant infectious diseases and underscores the importance of multidisciplinary management strategies for better patient outcomes. [Extracted from the article]

A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.

Background: Polyomavirus BK is one of the life-threatening infections in kidney transplant recipients. The activation of this virus can eventually lead to the loss of the graft. There are very few studies on the expression level of BK virus microRNAs. Therefore, in this study, we investigated the function of BK virus microRNAs and their effect on host cell microRNAs’ expression level. BK virus encodes two microRNAs, namely miR-B1-3p and miR-B1-5p. Therefore, it is crucial to study these microRNAs as markers of viral infection and their regulation. So far, there is no approved drug or vaccine to treat BK virus infection. Consequently, understanding the relationship between BK virus and host cell microRNAs is integral to the control of infection in kidney transplant patients. Materials and Methods: In this study, ten tissue samples from kidney transplant recipients with symptoms of BK virus nephropathy, ten urine samples from kidney transplant patients without active BK virus infection, and 20 healthy individuals were included. The expression level of the studied microRNAs was measured in all the samples using SYBR Green Real-time PCR. Results: The results showed that the expression level of the studied microRNAs, including miR-B1-3p, miR-B1-5p, miR-155, miR-520, miR-10b, miR-30a in the tissue samples of kidney transplant patients with BK virus nephropathy symptoms were significantly increased compared to kidney transplant patients without active BK virus infection. Conclusion: The assessment of some microRNAs, such as miR-520, miR-30a, and miR-B1-3p/5p, may assist in the prediction and prevention of BKPyV activation in KTRs, particularly in urine samples.

Background: BK virus (BKV) is the main cause of polyomavirus‐associated nephropathy in kidney transplant patients and hemorrhagic cystitis in bone marrow recipients. BKV quantitation by PCR is crucial in diagnostic and therapeutic management of transplant patients infected with BKV. We evaluated the performance of the Qiagen BKV ASR for the quantification of BKV on the NeuMoDx™ 96 System and compared the results to our standard of care (SOC) test, the Diasorin BKV ASR on the Liaison® MDX. Methods: The analytical performance was assessed using commercially available BKV Panels that meet the 1st WHO International Standards for BKV nucleic acid amplification techniques. The clinical performance was evaluated using 204 residual plasma and urine samples previously identified with the SOC assay. Results: The assay exhibited a strong linear correlation (R² = 0.9985) with the reference panel and an excellent analytical accuracy (R² = 0.9976). The LoD was determined to be 50 IU/mL with remarkable precision within and between days (SDEV 0.00—0.57 and 0.05—0.31, respectively). Of the 204 samples, only 10 (4.9 %) were discordant (PPA = 92.37 %; NPA = 100 %). Although the Qiagen BKV ASR quantified BKV DNA at an average of 0.48 Log IU/mL lower than the SOC, it showed a strong concordance to the SOC results. Compared to the SOC, the Qiagen BKV ASR had a more automated workflow, with less hands-on time, leading to quicker turnaround time. Conclusion: The Qiagen BKV ASR is specific, sensitive, and accurate in quantifying BKV in plasma and urine specimens on the fully automated NeuMoDx™ 96 System.

Summary: Background: BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control. Thus, understanding the composition and activity of the humoral anti-BKV responses in donor/recipient (D/R) pairs is critical. Methods: Using 224 paired pre-transplant D/R samples, BKV VP1 genotype-specific pseudoviruses were employed to define the breadth of the antibody response against different serotypes (ELISA) and, to characterise specific neutralising activity (nAb) using the 50% inhibitory concentration (LogIC50). Mismatch (MM) ratios were calculated using the ratio of recipient ELISA or nAb reactive BKV serotypes relative to the number of donor reactive serotypes. Findings: BKV DNAaemia was observed in 28/224 recipients of kidney transplants. These recipients had lower nAb titres against all the serotypes, with median logIC50 values of 1.19–2.91, compared to non-viraemic recipients’ median logIC50 values of 2.13–3.30. nAb D/R MM ratios >0.67 associated with significantly higher risk of BKV viraemia, with an adjusted odds ratio of 5.12 (95% CI 2.07 to 13.04; p

This article discusses the use of immune repertoire sequencing as a non-invasive and precise diagnostic method for kidney transplant rejection. The study enrolled 10 recipients with ambiguous diagnoses of transplant kidney dysfunction and used immune repertoire sequencing to classify patients into rejection and non-rejection categories. The sequencing results largely matched biopsy pathological results, with major clone expansions corresponding to rejection types. The study also demonstrated the potential of immune repertoire sequencing in monitoring treatment effectiveness and diagnosing refractory rejection. However, further research is needed to analyze patterns in immune repertoire changes associated with viral infections or calcineurin inhibitors toxicity. [Extracted from the article]