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1.
J Med Virol ; 96(6): e29742, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38874263

RESUMO

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.


Assuntos
Vírus BK , Genótipo , Vírus JC , Transplante de Rim , Epidemiologia Molecular , Infecções por Polyomavirus , Humanos , Vírus BK/genética , Vírus BK/isolamento & purificação , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/urina , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Vírus JC/genética , Vírus JC/isolamento & purificação , Estudos de Casos e Controles , Adulto , Eliminação de Partículas Virais , Idoso , Transplantados/estatística & dados numéricos , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/urina , DNA Viral/urina , DNA Viral/genética , Aloenxertos/virologia
2.
Sci Rep ; 14(1): 12855, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834615

RESUMO

BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The 'Reduction group' involved dose reduction of tacrolimus while the 'Conversion group' included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3-4 and 4-5). In the iVL 4-5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3-4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.


Assuntos
Vírus BK , Inibidores de Calcineurina , Imunossupressores , Transplante de Rim , Infecções por Polyomavirus , Serina-Treonina Quinases TOR , Tacrolimo , Viremia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores de Calcineurina/uso terapêutico , Viremia/tratamento farmacológico , Infecções por Polyomavirus/tratamento farmacológico , Tacrolimo/uso terapêutico , Adulto , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Imunossupressores/uso terapêutico , Carga Viral/efeitos dos fármacos , Resultado do Tratamento , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/virologia , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Sirolimo/uso terapêutico , República da Coreia , Estudos Retrospectivos , Idoso
3.
PLoS One ; 19(6): e0304147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861564

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the 7th most common cancer, accounting for 3.47% of male cancers and 3% of female cancers. However, there is currently a lack of information regarding the presence of PyVs and HPVs co-infection specifically in CRC cases in Egypt. Therefore, the aim of this study was to investigate the occurrence of HPVs and HPyVs (JCPyV, BKPyV, and SV40) infections, as well as co-infections, among CRC patients in Egypt. Additionally, the study aimed to assess any potential association between these viral infections and tumor stages. METHODS: In the present study, we analyzed a total of 51 tissue samples obtained from Egyptian CRC patients, along with 19 polyps' samples. Our investigation focused on the detection and genotyping of HPyVs using Real-Time PCR. Additionally, we employed real-time PCR for the detection of HPVs, and for their genotyping, we utilized a combination of PCR amplification followed by sequencing. RESULTS: In our study, we found evidence of HPyVs infection in the CRC patients, specifically SV40 (25.5%) and BKPyV (19.6%). However, JCPyV was not detected in the samples that were examined. Additionally, we discovered that HPV was present in 43.1% of the CRC patients. When considering viral co-infections, 19.6% of the CRC samples showed coexistence of multiple viruses, while no co-infections were found in the polyps samples. Importantly, we observed a significant correlation between the presence of HPVs and advanced colorectal tumor grades B2 and D. CONCLUSION: Our findings provide valuable data for the detection of oncogenic viruses in colorectal cancer (CRC) and underscore the association of viral co-infections with advanced tumor stages. However, further research with larger cohorts is necessary to validate these findings and strengthen their significance in the field of CRC.


Assuntos
Neoplasias Colorretais , Papillomaviridae , Infecções por Papillomavirus , Infecções por Polyomavirus , Polyomavirus , Humanos , Neoplasias Colorretais/virologia , Egito/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/complicações , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Polyomavirus/isolamento & purificação , Polyomavirus/genética , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Estudos de Casos e Controles , Coinfecção/virologia , Coinfecção/epidemiologia , Idoso , Adulto , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/complicações , Genótipo
4.
Pediatr Transplant ; 28(5): e14791, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38808701

RESUMO

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.


Assuntos
Vírus BK , Rejeição de Enxerto , Imunossupressores , Transplante de Rim , Infecções por Polyomavirus , Tacrolimo , Infecções Tumorais por Vírus , Humanos , Estudos Retrospectivos , Masculino , Feminino , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Criança , Tacrolimo/uso terapêutico , Imunossupressores/uso terapêutico , Infecções por Polyomavirus/sangue , Adolescente , Infecções Tumorais por Vírus/sangue , Infecções Tumorais por Vírus/imunologia , Pré-Escolar , DNA Viral/sangue , Lactente , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/virologia
5.
Clin Transplant ; 38(5): e15329, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38722085

RESUMO

BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.


Assuntos
Vírus BK , Rejeição de Enxerto , Sobrevivência de Enxerto , Testes de Função Renal , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Viremia , Humanos , Transplante de Rim/efeitos adversos , Vírus BK/imunologia , Vírus BK/isolamento & purificação , Feminino , Masculino , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/complicações , Pessoa de Meia-Idade , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Seguimentos , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Viremia/imunologia , Viremia/virologia , Prognóstico , Fatores de Risco , Taxa de Filtração Glomerular , Adulto , Complicações Pós-Operatórias , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Estudos Retrospectivos , Falência Renal Crônica/cirurgia , Falência Renal Crônica/imunologia , Nefropatias/virologia , Nefropatias/imunologia , Nefropatias/cirurgia , Transplantados
6.
Exp Clin Transplant ; 22(4): 267-269, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742316

RESUMO

OBJECTIVES: BK virus is a major cause of chronic renal allograft failure.Transplant ureteral stent use has been reported as a risk factorfor BK virus infection. Recently, the use of a new type of ureteral stent (Magnetic Black Star) was reported in kidney transplant recipients. The aim ofthis preliminary report was to compare BK virus viremia and viruria occurrence depending on the type of double-J stent (standard versus Magnetic Black Star). MATERIALS AND METHODS: We included all kidney transplants performed in our center from January to December 2022. Each case had double-J stent placement. Indwelling stents were either a 6- or 7-Fr standard double-J stent or a 6-Fr Magnetic Black Star double-J stent. The type of double-J stent was chosen according to the surgeon's preference. A standard BK virus screening protocol was followed during the study period, which consisted of routine polymerase chain reaction examination of plasma and urine samples during monthly follow-ups. RESULTS: We assessed 120 patients without missing data: 92 patients received standard double-J stents and 28 patients received Magnetic Black Star stents. Patients were mostly male in the standard group (70.7%) versus the Magnetic Black Star group (42.9%) (P = .01). ABO- and HLA-incompatible transplant rates were similar in both groups. BK viremia occurrence and BK viruria occurrence were similar between groups at 1 month, 3 months, and 6 months. CONCLUSIONS: This preliminary study showed no differences concerning BKvirus infection depending on the type of double-J stents used during kidney transplant.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Desenho de Prótese , Stents , Infecções Tumorais por Vírus , Viremia , Humanos , Transplante de Rim/efeitos adversos , Vírus BK/patogenicidade , Vírus BK/imunologia , Masculino , Viremia/diagnóstico , Viremia/virologia , Feminino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/urina , Fatores de Risco , Resultado do Tratamento , Adulto , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/urina , Fatores de Tempo , Dados Preliminares , Estudos Retrospectivos
7.
Genet Test Mol Biomarkers ; 28(5): 189-198, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38634609

RESUMO

Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.


Assuntos
Asbesto Crocidolita , Neoplasias Pleurais , Vírus 40 dos Símios , Humanos , Vírus 40 dos Símios/genética , China/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/virologia , Neoplasias Pleurais/genética , Mesotelioma/virologia , Mesotelioma/epidemiologia , Mesotelioma/genética , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Linhagem Celular Tumoral , Mesotelioma Maligno/genética , Neoplasias Pulmonares/virologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/epidemiologia , Adulto
8.
J Avian Med Surg ; 38(1): 7-14, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38686883

RESUMO

Avian polyomavirus (APV) infection causes various health problems in psittacine species, including death. The present study was conducted to investigate the prevalence of APV among psittacine birds in Iran. We also aimed to evaluate the impact of age, sex, species, season, and origin of the birds on the prevalence of APV. This study investigated the presence of APV among 1050 individual birds from 7 psittacine species over a 1-year period in Iran, namely, green-cheeked parakeets (Pyrrhura molinae), rosy-faced lovebirds (Agapornis roseicollis), monk parakeets (Myiopsitta monachus), sun conures (Aratinga solstitialis), Senegal parrots (Poicephalus senegalus), cockatiels (Nymphicus hollandicus), and grey parrots (Psittacus erithacus). The overall prevalence of APV in all studied species was 25% (263/1050, 95% confidence interval [CI]: 22.5-27.8). Results of the study showed that age and the season of the year were 2 important determinant factors in the prevalence of APV in psittacine birds. Young psittacine birds <6 months old were 2.94 (95% CI: 1.19-7.27) times more likely to be infected with APV than birds >1 year old, and there was a significant interaction between season and species in the multivariate analysis. In the winter season, rosy-faced lovebirds and green-cheeked parakeets were 15.6 (95% CI: 4.20-57.95) and 4.76 (95% CI: 1.4-16.21) times more likely to be infected with APV than in other seasons, respectively. This is the first report on the detection rate of APV in psittacine birds in Iran.


Assuntos
Doenças das Aves , Infecções por Polyomavirus , Polyomavirus , Psittaciformes , Animais , Irã (Geográfico)/epidemiologia , Doenças das Aves/epidemiologia , Doenças das Aves/virologia , Infecções por Polyomavirus/veterinária , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologia , Fatores de Risco , Masculino , Feminino , Polyomavirus/isolamento & purificação , Prevalência , Estações do Ano , Infecções Tumorais por Vírus/veterinária , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia
9.
Asian Pac J Cancer Prev ; 25(3): 821-827, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38546065

RESUMO

INTRODUCTION: Breast cancer, a pervasive invasive carcinoma among women globally, afflicts approximately 12% of women worldwide. Previous studies have indicated that certain viruses, including oncogenic viruses such as polyomaviruses BK and JC, may play a role in the development of breast cancer. In light of this, the present study endeavors to assess the incidence of BKV and JCV virus in breast cancer patients. MATERIALS AND METHODS: One hundred formalin-fixed paraffin-embedded tissue samples were procured and subjected to deparaffinize by xylene, followed by DNA extraction through the phenol-chloroform methodology. Detection and genotyping of BKV and JCV were carried out utilizing specific primers via PCR analysis. RESULTS: Merely 2 out of 100 (2%) ductal carcinoma in situ with grade 2 specimens exhibited positivity for BK virus genotype IV, whereas JC virus DNA was not discerned across all the samples. DISCUSSION: The findings of the current investigation demonstrate that there was an absence of JC virus detection in the breast biopsy. Additionally, a small fraction of patients diagnosed with ductal carcinoma exhibited a low prevalence of genotype IV polyomavirus BK at a rate of 2%. However, in order to gain a more comprehensive understanding of the incidence of BKV and JCV in breast cancer, a substantial number of breast samples must undergo investigation.


Assuntos
Vírus BK , Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Vírus JC , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Feminino , Vírus JC/genética , Neoplasias da Mama/epidemiologia , Prevalência , Infecções por Polyomavirus/epidemiologia , DNA Viral/genética , DNA Viral/análise , Vírus BK/genética , Infecções Tumorais por Vírus/epidemiologia
11.
Ann Hematol ; 103(5): 1737-1744, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38509389

RESUMO

Although it is known that BK polyomavirus (BKPyV) causes hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of BKPyV viremia has not been fully evaluated. We retrospectively analyzed the results of quantitative polymerase chain reaction (PCR) evaluations for detecting BKPyV in the whole blood samples of patients undergoing allogeneic HSCT during the period from January 2010 to June 2020 at a single institute, Tokyo Medical and Dental University. BKPyV was detected in the blood of 28 of the 107 evaluated patients, and the cumulative incidence of was 27.9% (95%CI: 20.2-37.9%). HC due to BKPyV developed in four of the 28 patients with BKPyV viremia (14.3%) and in two of the 79 patients without it (2.5%; P < 0.05). BKPyV viremia itself did not affect the patients' post-transplant estimated glomerular filtration rate (eGFR), but BKPyV viremia with a high viral load was significantly associated with decreased eGFR values (P < 0.05). BKPyV viremia was also associated with significantly lower progression-free survival at 3 years (35.1% [95%CI: 17.8-53.1%] vs. 60.4% [95%CI: 48.4-70.5], P < 0.05). Our findings demonstrated that BKPyV viremia was associated with onset of HC, an early decline of renal function, and poorer survival after allogeneic HSCT. Further studies are needed to test these results and elucidate the mechanisms of renal dysfunction associated with BKPyV viremia.


Assuntos
Vírus BK , Cistite Hemorrágica , Cistite , Transplante de Células-Tronco Hematopoéticas , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Estudos Retrospectivos , Viremia/complicações , Infecções por Polyomavirus/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Tumorais por Vírus/epidemiologia
12.
J Clin Microbiol ; 62(4): e0135423, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38526061

RESUMO

BK virus (BKV) infection or reactivation in immunocompromised individuals can lead to adverse health consequences including BKV-associated nephropathy (BKVAN) in kidney transplant patients and BKV-associated hemorrhagic cystitis (BKV-HC) in allogeneic hematopoietic stem cell transplant recipients. Monitoring BKV viral load plays an important role in post-transplant patient care. This study evaluates the performance of the Alinity m BKV Investigational Use Only (IUO) assay. The linearity of the Alinity m BKV IUO assay had a correlation coefficient of 1.000 and precision of SD ≤ 0.25 Log IU/mL for all panel members tested (2.0-7.3 Log IU/mL). Detection rate at 50 IU/mL was 100%. Clinical plasma specimens tested comparing Alinity m BKV IUO to ELITech MGB Alert BKV lab-developed test (LDT) on the Abbott m2000 platform using specimen extraction protocols for DNA or total nucleic acid (TNA) resulted in coefficient of correlation of 0.900 and 0.963, respectively, and mean bias of 0.03 and -0.54 Log IU/mL, respectively. Alinity m BKV IUO compared with Altona RealStar BKV and Roche cobas BKV assays demonstrated coefficient of correlation of 0.941 and 0.980, respectively, and mean bias of -0.47 and -0.31 Log IU/mL, respectively. Urine specimens tested on Alintiy m BKV IUO and ELITech BKV LDT using TNA specimen extraction had a coefficient of correlation of 0.917 and mean bias of 0.29 Log IU/mL. The Alinity m BKV IUO assay was performed with high precision across the dynamic range and correlated well with other available BKV assays. IMPORTANCE: BK virus (BKV) in transplant patients can lead to adverse health consequences. Viral load monitoring is important in post-transplant patient care. This study evaluates the Alinity m BKV assay with currently available assays.


Assuntos
Vírus BK , Transplante de Rim , Ácidos Nucleicos , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Vírus BK/genética , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/diagnóstico , Carga Viral/métodos , Infecções Tumorais por Vírus/diagnóstico
13.
Exp Dermatol ; 33(3): e15062, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38532566

RESUMO

Merkel cell carcinoma (MCC) is a high-grade skin cancer, but spontaneous regression is observed at a markedly higher frequency than in other carcinomas. Although spontaneous regression is a phenomenon that greatly impacts treatment planning, we still cannot predict it. We previously reported on the prognostic impact of the presence or absence of tertiary lymphoid structures (TLS) and of Merkel cell polyomavirus (MCPyV) infection. To learn more about the spontaneous regression of MCC, detailed analyses were performed focusing on spontaneous regression cases. We collected 71 Japanese patients with MCC including 6 cases of spontaneous regression. Samples were analysed by immunostaining, spatial single-cell analysis using PhenoCycler, and RNA sequencing using the next-generation sequencer (NGS). All 6 cases of spontaneous regression were positive for MCPyV. TLS was positive in all 5 cases analysed. Spatial single-cell analyses revealed that PD-L1-positive tumour cells were in close proximity to CD20-positive B cell and CD3-, 4-positive T cells. Gene set enrichment analysis between MCPyV-positive and TLS-positive samples and other samples showed significantly high enrichment of "B-cell-mediated immunity" gene sets in the MCPyV-positive and TLS-positive groups. In conclusion, TLS may play an important role in the spontaneous regression of MCC.


Assuntos
Carcinoma de Célula de Merkel , Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Neoplasias Cutâneas , Estruturas Linfoides Terciárias , Infecções Tumorais por Vírus , Humanos , Carcinoma de Célula de Merkel/patologia , Neoplasias Cutâneas/patologia , Remissão Espontânea , Infecções Tumorais por Vírus/patologia , Infecções por Polyomavirus/patologia , Poliomavírus das Células de Merkel/genética
14.
Biomolecules ; 14(3)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38540767

RESUMO

Mitochondria are essential organelles that possess their own DNA. Mitochondrial dysfunction has been revealed in many kidney diseases, including BK polyomavirus-associated nephropathy (BKPyVAN). In this study, we introduce an innovative approach for non-invasive monitoring of mitochondrial impairment through urinary donor-derived cell-free mitochondrial DNA (ddcfmtDNA), addressing the crucial challenge of BKPyVAN diagnosis. Urinary samples were collected at the time of biopsy from a total of 60 kidney transplant recipients, comprising 12 with stable function, 22 with T cell-mediated rejection, and 21 with biopsy-proven BKPyVAN. Our findings reveal that the ddcfmtDNA-to-ddcfDNA ratio exhibits superior capability in distinguishing BKPyVAN from other conditions, with a cutoff value of 4.96% (area under curve = 0.933; sensitivity: 71.4%; and specificity: 97.1%). Notably, an elevation of ddcfmtDNA levels is associated with mitochondrial damage, as visualized through electron microscopy. These results underscore the promise of non-invasive monitoring for detecting subtle mitochondrial damage and its potential utility in BKPyVAN diagnosis. Further investigations are required to advance this field of research.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Transplante de Rim/efeitos adversos , Vírus BK/genética , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/patologia , Rejeição de Enxerto , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/patologia , Mitocôndrias/genética , DNA Mitocondrial/genética
15.
Transpl Infect Dis ; 26(2): e14260, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38547002

RESUMO

INTRODUCTION: As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking. METHODS: We performed a retrospective monocenter study on 64 patients diagnosed with biopsy-proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily. RESULTS: Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes. CONCLUSION: No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology.


Assuntos
Vírus BK , Nefropatias , Nefrite Intersticial , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Estudos Retrospectivos , Nefrite Intersticial/patologia , Aloenxertos/patologia , Inflamação , Esteroides/uso terapêutico , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Rejeição de Enxerto/tratamento farmacológico
17.
Microbiol Immunol ; 68(5): 179-184, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38433377

RESUMO

BK polyomavirus (BKPyV) was the first human polyomavirus to be isolated from an immunosuppressed kidney transplant recipient in 1971. BKPyV reactivation causes BKPyV-associated nephropathy and hemorrhagic cystitis. However, the mechanisms underlying BKPyV replication remain unclear. In the present study, we performed the long-term cultivation of COS-7 cells transfected with archetype KOM-5 DNA, which were designated as COS-BK cells. BKPyV derived from COS-BK cells was characterized by analyzing the amount of the virus based on hemagglutination, viral replication, and the production of viral protein 1 (VP1). Immunostaining showed that VP1-positive cells accounted for a small percentage of COS-BK cells. The nucleotide sequences encompassing the origin of the DNA replication of BKPyV derived from COS-BK cells were generated from KOM-5 by the deletion of an 8-bp sequence, which did not involve T antigen binding sites. BKPyV replicated most efficiently in COS-BK cells in DMEM containing 2% fetal bovine serum. These results indicate that COS-BK cells are a suitable culture system for studying the persistent infection of archetype BKPyV.


Assuntos
Vírus BK , Infecções por Polyomavirus , Replicação Viral , Vírus BK/fisiologia , Vírus BK/genética , Animais , Chlorocebus aethiops , Células COS , Infecções por Polyomavirus/virologia , Humanos , Proteínas do Capsídeo/genética , DNA Viral/genética , Infecção Persistente/virologia , Antígenos Virais de Tumores/genética , Infecções Tumorais por Vírus/virologia
20.
Transpl Infect Dis ; 26(2): e14237, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341645

RESUMO

BACKGROUND: BK polyomavirus (BKV) can cause permanent loss of allograft function due to BKV-associated nephropathy (BKVN) in kidney transplant recipients. Besides immunosuppression reduction, there are no consistently effective interventions for BKV infection. Study purpose was to define natural history of BKV infection, identify risk factors for BKV reactivation and BKVN in kidney transplant recipients, and inform the design/conduct of future clinical trials of BKV-targeted therapeutics. METHODS: We conducted a multicenter prospective observational study of incident kidney transplant recipients at six U.S. transplant centers. Participants were monitored every 4 weeks for BKV reactivation and followed for up to 24 months post-transplant. We used regression models (logistic, survival, mixed models) to study relationships between BK viremia/BKVN, clinical characteristics, and allograft function. RESULTS: We enrolled 335 participants. Fifty-eight (17%) developed BK viremia, 6 (2%) developed biopsy-proven BKVN, and 29 (9%) developed suspected/presumed BKVN (defined as BKV viral load > 10,000 copies/mL without biopsy). Male donor sex was associated with lower odds for BK viremia, whereas recipient Black race was associated with two-fold increased odds for BK viremia. Recipient female sex was associated with more rapid clearance of BK viremia. Persistent BK viremia/BKVN was associated with poorer allograft function by 24 months post-transplant. CONCLUSIONS: We identified multiple donor and recipient demographic factors associated with risk for BKV infection and poorer allograft function by 24 months post-transplant. This may help design future clinical trials of therapies to prevent or mitigate the deleterious impact of BKV reactivation on kidney transplant outcomes.


Assuntos
Vírus BK , Nefropatias , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Masculino , Feminino , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Viremia/complicações , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/tratamento farmacológico
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