RESUMO
Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine cutaneous carcinoma with a high mortality rate. The MCC etiology is not fully understood. Merkel cell-associated polyomavirus (MCPyV) was found in MCC patients, indicating a risk factor for the tumor. Caucasian, elderly, and immunocompromised individuals are more likely to develop this tumor. HLA-G consists of a non-classical class I (Ib) HLA molecule with an immunoregulatory function and was associated with tumor escape in different types of tumors, nonetheless, never been studied in MCC. The purpose of this study was to evaluate the HLA-G expression and also to detect the MCPyV in MCC patients and correlate it with the clinical course of the disease. Forty-five MCC patients were included in a retrospective study. Formalin-fixed paraffin-embedded cutaneous skin biopsies were used by immunohistochemistry and RT-PCR to verify the HLA-G expression and MCPyV infection. HLA-G expression was found in 7 (15.6%), while the presence of MCPyV was detected in 28 (62.2%) of the studied patients. No significant association was found between HLA-G expression and MCPyV infection (p = 0.250). The presence of MCPyV was associated with areas of low sunlight exposure (p = 0.042) and the HLA-G expression with progression to death (p = 0.038). HLA-G expression was detected in MCC patients, as well as the MCPyV presence was confirmed. These markers could represent factors with a possible impact on patient survival; however, further studies with a greater number of patients are needed, to better elucidate the possible role in disease progression.
Assuntos
Carcinoma de Célula de Merkel , Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Neoplasias Cutâneas , Humanos , Idoso , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/patologia , Poliomavírus das Células de Merkel/genética , Antígenos HLA-G , Neoplasias Cutâneas/genética , Estudos Retrospectivos , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/genéticaRESUMO
Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells, as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the "cytopathic-inflammatory pathology pattern" proposed in the pathogenesis of Human polyomavirus-1-associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing a cytopathic effect in Madin-Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed.
Assuntos
Transplante de Rim , Nefrite Intersticial , Infecções por Polyomavirus , Polyomavirus , Infecções Tumorais por Vírus , Animais , Anticorpos Monoclonais , Antígenos Virais de Tumores , Bovinos , Feto/patologia , Humanos , Rim , Transplante de Rim/efeitos adversos , Nefrite Intersticial/complicações , Nefrite Intersticial/patologia , Infecções por Polyomavirus/complicações , Vírus 40 dos Símios , Infecções Tumorais por Vírus/complicaçõesRESUMO
BK virus nephropathy in kidney transplantation is widely recognized as an important cause of graft dysfunction and loss. In the case of transplants of organs other than kidney, BK virus nephropathy in native kidneys has been recognized as a cause of chronic kidney disease, which is related with immunosuppression; however, the diagnosis is usually late because the renal dysfunction is attributed to other causes, such as toxicity by anticalcineurinic drugs, interstitial nephritis due to medications, hemodynamic changes, diabetes, hypertension, etc. We report a case of BK virus nephropathy in a patient who underwent heart transplantation due to peripartum cardiomyopathy. The kidney biopsy reported active chronic tubulointerstitial nephritis associated with late stage polyomavirus nephritis and the blood viral load for BK virus was positive (logarithm 4.5). The immunosuppressive treatment was reduced, and after two years of follow-up, the patient had stable renal function with a serum creatinine of 2.5 mg/dL (GFR of 23.4 mL/min/1.73m2). We recommend that the BK virus be considered as a cause of renal dysfunction in heart transplant recipients, with the aim of detecting its replication in time to reduce immunosuppressive therapy before irreversible compromise of renal function may manifest.
Assuntos
Vírus BK , Transplante de Coração , Nefrite Intersticial , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Imunossupressores , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnósticoRESUMO
BACKGROUND: BK polyomavirus-associated nephropathy (PyVAN) is an important complication after kidney transplantation. Prevalence ranges from 1% to 10%, and graft loss occurs in approximately 50% of the cases. There is no effective treatment, so early viral detection with immunosuppression tapering is the current strategy to prevent PyVAN. AIMS: To verify the frequency of PyVAN in a single center and evaluate the response to immunosuppressive adjustments through graft survival analysis. METHODS: Retrospective evaluation of a cohort of kidney transplant recipients with biopsy-proven PyVAN, compared with no-PyVAN patients regarding clinical aspects, immunosuppression, and graft survival over at least 2 years. RESULTS: There were 1404 kidney transplants analyzed in the study period, 58 with biopsy-proven PyVAN. Cumulative incidence was 4.1%. Median time from transplantation to PyVAN diagnosis was 6 (1-41) months. PyVAN was associated with recipient male gender (P = .041) and deceased donation (P = .005). Graft survival was inferior for PyVAN compared to no-PyVAN patients, 81.8% vs 75.2%, P = .019. Thirteen (22.4%) PyVAN patients lost their grafts, nine (15.5%) losses attributed to BKPyV infection. Three patients with BKPyV-associated graft losses were submitted to a successful second kidney transplant, with no evidence of viral replication during follow-up. CONCLUSION: PyVAN still is an important cause of kidney graft failure. Even though implementing active vigilance and immunosuppressive adjustment, this real-life single-center study demonstrated inferior graft survival in PyVAN patients compared to non-PyVAN.
Assuntos
Rejeição de Enxerto/virologia , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Adulto , Vírus BK/patogenicidade , Feminino , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão/efeitos adversos , Rim/patologia , Rim/virologia , Nefropatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Estudos Retrospectivos , Fatores Sexuais , Transplante Homólogo/efeitos adversos , Infecções Tumorais por Vírus/complicações , Viremia , Adulto JovemRESUMO
La tricodisplasia espinulosa es una patología viral infrecuente causada por un tipo de poliomavirus, el cual se da siempre en contexto de inmunosupresión. Existen reportes que estiman una seroprevalencia en adultos de 70%, y hasta 90% en inmu-nocomprometidos. El cuadro clínico se caracteriza por pápulas color piel hiperqueratósicas en zonas centro faciales, orejas y tronco, asintomáticas o con prurito escaso. Existen métodos de confirmación diagnóstica como PCR o test de Elisa, que no se encuentran disponibles en Chile. Por lo tanto, en nuestro contexto el estudio histopatológico es fun-damental, dada su accesibilidad y que los hallazgos de la biopsia son característicos. El manejo debe siempre considerar, de ser posible, disminuir la in-munosupresión del paciente. Otras medidas son: extracción manual de las lesiones y aplicación de cidofovir o valganciclovir tópicos
Trichodysplasia spinulosa is an infrequent viral pathology caused by a type of polyomavirus, which always occurs in context of immunosuppression. There are reports that estimate sero-prevalence in adults of 70%, and 90% in immunocompromised. Patients have numerous, mildly pruritic, folliculocentric, flesh-colored to pink papules with central keratinaceous spines. There are methods of diagnostic confirmation such as PCR or Elisa test, not available in Chile. The-refore, in our context the histopathological study is fundamental because biopsy findings are cha-racteristic. Management should always consider, if possible, decrease the immunosuppression of the patient. Other measures consist of manual extraction and cidofovir or topical valganciclovir.
Assuntos
Humanos , Feminino , Pré-Escolar , Dermatopatias/complicações , Dermatopatias/patologia , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Dermatopatias/diagnóstico , Hospedeiro Imunocomprometido , Infecções por Polyomavirus/diagnósticoRESUMO
Introducción: El carcinoma de células de Merkel (MCC) es un tumor cutáneo maligno agresivo y de mal pronóstico. La incidencia es mayor en adultos hombres, caucásicos, con edad promedio de 70 años. Feng et al, lograron aislar un nuevo virus en muestras de este tumor, que denominaron virus polioma de células de Merkel (MCPyV). Se ha intentado establecer una relación causal entre el virus y MCC. El virus está integrado al genoma y produciría mutaciones específicas. En muestras de MCC, se ha detectado expresión de oncoproteinas virales (antígenos T) que promueven la replicación viral y tumorogénesis
Introduction: Merkel cell carcinoma (MCC) is an aggressive malignant cutaneous tumor with poor prognosis. Most cases affect elder patient with an average of 70 years of age. Feng et al isolated a new virus, the Merkel cell carcinoma polyoma virus (MCPyV). A causal relationship between MCPyV y MCC has been established. The virus is integrated in the genome and pro-duces specific mutations. MCC samples show ex-pression of viral oncoproteins (T antigens) that promote viral replication and tumorogenesis.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/virologia , Infecções por Polyomavirus/complicações , Prognóstico , Neoplasias Cutâneas/metabolismo , Imuno-Histoquímica , Carcinoma de Célula de Merkel/metabolismo , Queratina-20/metabolismoRESUMO
The BK virus (BKV) produces a subclinical kidney infection in immunocompetent individuals. However, viremia may occur in kidney transplant patients with ongoing immunosuppression. BKV-associated nephropathy (BKVN) has no specific treatment and is a leading cause of organ transplant loss. In this study, we evaluated the predisposition and the clinical impact of BKV replication in kidney transplant patients during post-transplant monitoring in a reference institution in Brazil. Demographic, clinical and laboratory data generated during routine outpatient follow-up were retrospectively collected. BK viremia was investigated using real-time polymerase chain reaction. Of the 553 participants, 7.4% (n = 41) presented BKV replication. Of these, 16 (39%) lost their kidney graft and interstitial nephritis was identified on kidney biopsy in 50% of the cases. Among the evaluated variables, only the use of the immunosuppressant mycophenolate sodium was identified as a risk factor for viremia (OR 7.96; 95% CI 2.35 to 26.98). The graft survival estimate in BKV-positive patients was significantly reduced (24.8% vs. 85.6%) after 10 years of transplantation. We concluded that defining predisposing factors remains an important challenge for the prevention and control of BKV activity following kidney transplantation, especially considering the development of BKVN and its strong effect on graft maintenance.
Assuntos
Vírus BK/fisiologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Viremia/complicações , Replicação Viral/imunologia , Adulto , Estudos Transversais , Feminino , Rejeição de Enxerto , Humanos , Masculino , Infecções por Polyomavirus/virologia , Estudos Retrospectivos , Fatores de Risco , Infecções Tumorais por Vírus/virologia , Viremia/virologiaRESUMO
ABSTRACT The BK virus (BKV) produces a subclinical kidney infection in immunocompetent individuals. However, viremia may occur in kidney transplant patients with ongoing immunosuppression. BKV-associated nephropathy (BKVN) has no specific treatment and is a leading cause of organ transplant loss. In this study, we evaluated the predisposition and the clinical impact of BKV replication in kidney transplant patients during post-transplant monitoring in a reference institution in Brazil. Demographic, clinical and laboratory data generated during routine outpatient follow-up were retrospectively collected. BK viremia was investigated using real-time polymerase chain reaction. Of the 553 participants, 7.4% (n = 41) presented BKV replication. Of these, 16 (39%) lost their kidney graft and interstitial nephritis was identified on kidney biopsy in 50% of the cases. Among the evaluated variables, only the use of the immunosuppressant mycophenolate sodium was identified as a risk factor for viremia (OR 7.96; 95% CI 2.35 to 26.98). The graft survival estimate in BKV-positive patients was significantly reduced (24.8% vs. 85.6%) after 10 years of transplantation. We concluded that defining predisposing factors remains an important challenge for the prevention and control of BKV activity following kidney transplantation, especially considering the development of BKVN and its strong effect on graft maintenance.
Assuntos
Humanos , Masculino , Feminino , Adulto , Infecções Tumorais por Vírus/complicações , Viremia/complicações , Replicação Viral/imunologia , Transplante de Rim/efeitos adversos , Vírus BK/fisiologia , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/virologia , Viremia/virologia , Estudos Transversais , Estudos Retrospectivos , Fatores de Risco , Infecções por Polyomavirus/virologia , Rejeição de EnxertoRESUMO
Infection with polyomavirus (BK virus) is the cause of renal graft losses in more than 50% of the infected cases. There should be a high index of suspicion about this disease, although the incidence is only between 2% and 5% as the future of renal graft depends on the early and appropriate management of the same. Herein, we describe three clinical cases: Two were those of kidney transplant and the third, a combined kidney-pancreas transplant. In these cases, by reducing immunosuppression and, in one case, replacing the calcineurin inhibitor by MTOR (mammalian target of rapamycin) in addition, we were able to preserve of the normal function of the transplanted organs.
Assuntos
Vírus BK , Imunossupressores/efeitos adversos , Necrose do Córtex Renal/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/efeitos adversosRESUMO
PURPOSE: John Cunningham (JC) viral DNA sequence has seldom been reported in patients with brain tumors such as high grade gliomas and medulloblastomas, pointing to a role in the etiopathogenesis of such tumors. RESULTS: We present a unique clinical case of an HIV-positive pediatric patient with multifocal leukoencephalopathy and confirmed JC virus (JCV) infection that developed a giant-cell glioblastoma. CONCLUSIONS: Experimental data with infected primates has previously hypothesized an association of human giant-cell glioblastoma with JCV or progressive multifocal leukoencephalopathy, though such association has not been documented in the literature for humans. Future studies with larger cohorts and molecular pathological analyses are still needed to corroborate the role of the widely spread human neurotropic virus in early transformation and in the development of brain tumors with different histology in the setting of HIV-related severe immunosuppression.