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1.
Virol J ; 19(1): 153, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-36163265

RESUMO

BACKGROUND: JC polyomavirus (JCPyV) is known to induce solid tumors such as astrocytomas, glioblastomas, and neuroblastomas in experimental animals, and recent studies have shown that the virus may be correlated with carcinogenesis. This study aimed to evaluate the impact of JCPyV on the progression of papillary thyroid cancer (PTC). METHODS: A total of 1057 samples, including 645 paraffin-embedded PTC biopsy samples (PEBS) and 412 fresh biopsy samples (FBS), and 1057 adjacent non-cancerous samples were evaluated for the presence of JCPyV DNA and RNA. RESULTS: We observed that 10.8% (114/1057) samples, including 17.5% (72/412) FBS and 6.5% (42/645) PEBS were positive for the JCPyV DNA. Among the JCPyV-positive samples, the mean JCPyV copy number was lower in patients with PEBS (0.3 × 10-4 ± 0.1 × 10-4 copies/cell) compared to FBS (1.8 × 10-1 ± 0.4 × 10-1 copies/cell) and non-PTC normal samples (0.2 × 10-5 ± 0.01 × 10-5 copies/cell), with a statistically significant difference (P < 0.001). The LT-Ag RNA expression was lower in PEBS than in FBS, while no VP1 gene transcript expression was found. CONCLUSIONS: Although our results confirmed the presence of JCPyV in some Iranian patients with PTC, more research is needed to verify these results.


Assuntos
Vírus JC , Infecções por Polyomavirus , Neoplasias da Glândula Tireoide , Humanos , Irã (Geográfico) , Vírus JC/genética , RNA , Câncer Papilífero da Tireoide
2.
Viruses ; 14(9)2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36146876

RESUMO

Since the non-coding control region (NCCR) and microRNA (miRNA) could represent two different and independent modalities of regulating JC polyomavirus (JCPyV) replication at the transcriptional and post-transcriptional levels, the interplay between JC viral load based on NCCR architecture and miRNA levels, following JCPyV infection with archetypal and rearranged (rr)-NCCR JCPyV variants, was explored in COS-7 and SVGp12 cells infected by different JCPyV strains. Specifically, the involvement of JCPyV miRNA in regulating viral replication was investigated for the archetypal CY strain-which is the transmissible form-and for the rearranged MAD-1 strain, which is the first isolated variant from patients with progressive multifocal leukoencephalopathy. The JCPyV DNA viral load was low in cells infected with CY compared with that in MAD-1-infected cells. Productive viral replication was observed in both cell lines. The expression of JCPyV miRNAs was observed from 3 days after viral infection in both cell types, and miR-J1-5p expression was inversely correlated with the JCPyV replication trend. The JCPyV miRNAs in the exosomes present in the supernatants produced by the infected cells could be carried into uninfected cells. Additional investigations of the expression of JCPyV miRNAs and their presence in exosomes are necessary to shed light on their regulatory role during viral reactivation.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , MicroRNAs , DNA Viral/genética , Humanos , Vírus JC/genética , MicroRNAs/genética , Carga Viral , Replicação Viral
3.
BMC Neurol ; 22(1): 306, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986243

RESUMO

BACKGROUND: Fingolimod is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML); however, its discontinuation may cause severe immune reconstitution inflammatory syndrome (IRIS). As both of these conditions (especially fingolimod induced PML) are rarely described in medical case reports distinguishing between PML-IRIS and MS-IRIS may be diagnostically challenging. CASE PRESENTATION: We report a patient with severe clinical decline (Expanded Disability Status Scale (EDSS) increasing from 3.5 to 7.5) and multiple, large, contrast-enhancing lesions on brain magnetic resonance imaging (MRI) a few months after fingolimod withdrawal. The diagnostic possibilities included IRIS due to fingolimod withdrawal versus PML-IRIS. The JC virus (JCV) antibody index was positive (2.56); however, cerebrospinal fluid (CSF) JCV real-time polymerase chain reaction (JCV-PCR) was negative and brain biopsy was not performed. After a long course of aggressive treatment (several pulsed methylprednisolone infusions, plasmapheresis, intravenous dexamethasone, oral mirtazapine) the patient gradually recovered (EDSS 2.5) and MRI lesions decreased. CONCLUSIONS: This case report demonstrates the importance of monitoring patients carefully after the discontinuation of fingolimod for PML-IRIS and rebound MS with IRIS as these conditions may manifest similarly.


Assuntos
Síndrome Inflamatória da Reconstituição Imune , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cloridrato de Fingolimode/efeitos adversos , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Imageamento por Ressonância Magnética , Natalizumab/efeitos adversos
4.
Virol J ; 19(1): 131, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941650

RESUMO

BACKGROUND AND AIMS: The John Cunningham virus (JCV) is the established etiological agent of the polyomavirus-associated nephropathy among renal transplant recipients. In the present study, we aimed to determine the probable predictive factors leading to JCV replication in renal transplant patients. MATERIAL AND METHODS: Urine and plasma samples were collected from a total of 120 consecutive renal-transplanted patients without preliminary screening from Jan 2018 to Mar 2019. After DNA extraction, the simultaneous detection and quantification of JCV and BK polyomavirus (BKV) were conducted using a Real-time quantitative PCR method. Moreover, statistical analyses were performed using the statistical software packages, SPSS version 21. RESULTS: The prevalence of JCV viruria and viremia among renal transplant recipients were 26 (21.67%) and 20 (16.67%), respectively. A significant association was observed between the JCV and two risk factors, diabetes mellitus (P = 0.002) and renal stones (P = 0.015). The prevalence of JCV viremia among recipients who were grafted near time to sampling was significantly higher (P = 0.02). There was a statistically significant coexistence between BK and JC viruses among our patients (P = 0.029). The frequency of JCV viruria in males was reported almost three times more than in females (P = 0.005). The JCV shedding in urine was significantly associated with the tropical steroids like prednisolone acetate, which have been the standard regimen (P = 0.039). Multivariable analysis revealed duration of post-transplantation (OR, 0.89; P = 0.038), diabetes mellitus (OR, 1.85; P = 0.034), and renal stone (OR 1.10; P = 0.04) as independent risk factors associated with JCV viremia post-renal transplantation. CONCLUSION: It seems that the discovery of potential risk factors, including immunological and non-immunological elements, may offer a possible preventive or therapeutic approach in the JCV disease episodes. The results of this study may also help clarify the probable clinical risk factors involving in progressive multifocal leukoencephalopathy development.


Assuntos
Vírus BK , Vírus JC , Nefropatias , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , DNA Viral/genética , Feminino , Humanos , Vírus JC/genética , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Masculino , Transplantados , Viremia/epidemiologia
6.
Eur J Med Res ; 27(1): 127, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35859146

RESUMO

INTRODUCTION: The human JC polyomavirus (JCPyV) has been detected in colorectal cancer (CRC) tissues and is suggested to contribute to CRC tumorigenesis. The rearrangement of the JCPyV regulatory region is supposedly associated with CRC development. The progression of CRC involves the stepwise accumulation of mutations. The large tumor antigen (LT) of JCPyV can trigger uncontrolled cell cycle progression by targeting oncogenes, and tumor suppressor genes, and causing chromosome instability. Few studies have focused on the presence of JCPyV DNA in the higher grade of CRC tissues. METHODS: We collected 95 tissue blocks from samples of stages I, II, III, and IV CRC. Nested PCR targeting the regulatory region of the viral genome was performed to determine the presence of JCPyV DNA in the various stages of colorectal cancer tissues. RESULTS: The nested PCR results showed that the positive rate of JCPyV DNA increased with the progression of CRC stages. The archetypal-like, non-rearrangement genotype of JCPyV with subtle mutations was the major genotype found in CRC samples. CONCLUSIONS: This finding in our study suggests that there may be an association between JCPyV and CRC progression.


Assuntos
Neoplasias Colorretais , Vírus JC , Infecções por Polyomavirus , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , DNA Viral/genética , Humanos , Incidência , Vírus JC/genética , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/epidemiologia , Taiwan/epidemiologia
7.
Mult Scler Relat Disord ; 65: 103995, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35810718

RESUMO

BACKGROUND: Natalizumab is a humanized monoclonal antibody used for treatment of highly active relapsing-remitting multiple sclerosis (MS). With more than 15 years of post-marketing experience with natalizumab in Canada, several real-world studies have shown the long-term efficacy and safety of natalizumab. In addition, risk stratification/mitigation strategies for progressive leukoencephalopathy (PML), an adverse effect associated with natalizumab based on the John Cunningham virus (JCV) index; treatment duration beyond 24 months; and prior exposure to immunosuppressant drugs have been developed. METHODS: A group of neurologists from various MS clinics across Canada met in September 2021 to update the 2015 Canadian practice recommendations for the use of natalizumab in persons with MS (PwMS). RESULTS: The recommendations focused on the long-term efficacy and safety data from real-world studies, patient selection according to JCV index criteria, risk management strategies for PML (including extended interval dosing), and options for switching to currently available disease-modifying therapies for MS. CONCLUSIONS: The recommendations of clinical neurologists seek to optimize the management of PwMS who may benefit from treatment with natalizumab.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Canadá , Humanos , Fatores Imunológicos/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Esclerose Múltipla/induzido quimicamente , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/efeitos adversos
8.
Viruses ; 14(6)2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35746716

RESUMO

BACKGROUND: Lytic infection of oligodendrocytes by the human JC polyomavirus (JCPyV) results in the demyelinating disease called progressive multifocal leukoencephalopathy (PML). The detection of viral DNA in the cerebrospinal fluid (CSF) by PCR is an important diagnostic tool and, in conjunction with defined radiological and clinical features, can provide diagnosis of definite PML, avoiding the need for brain biopsy. The main aim of this study is to compare the droplet digital PCR (ddPCR) assay with the gold standard quantitative PCR (qPCR) for the quantification of JC viral loads in clinical samples. METHODS: A total of 62 CSF samples from 31 patients with PML were analyzed to compare the qPCR gold standard technique with ddPCR to detect conserved viral DNA sequences in the JCPyV genome. As part of the validation process, ddPCR results were compared to qPCR data obtained in 42 different laboratories around the world. In addition, the characterization of a novel triplex ddPCR to detect viral DNA sequence from both prototype and archetype variants and a cellular housekeeping reference gene is described. Triplex ddPCR was used to analyze the serum from six PML patients and from three additional cohorts, including 20 healthy controls (HC), 20 patients with multiple sclerosis (MS) who had never been treated with natalizumab (no-NTZ-treated), and 14 patients with MS who were being treated with natalizumab (NTZ-treated); three from this last group seroconverted during the course of treatment with natalizumab. RESULTS: JCPyV DNA was detected only by ddPCR for 5 of the 62 CSF samples (8%), while remaining undetected by qPCR. For nine CSF samples (15%), JCPyV DNA was at the lower limit of quantification for qPCR, set at <250 copies/mL, and therefore no relative quantitation could be determined. By contrast, exact copies of JCPyV for each of these samples were quantified by ddPCR. No differences were observed between qPCR and ddPCR when five standardized plasma samples were analyzed for JCPyV in 42 laboratories in the United States and Europe. JCPyV-DNA was undetected in all the sera from HC and MS cohorts tested by triplex ddPCR, while serum samples from six patients with PML tested positive for JCPyV. CONCLUSION: This study shows strong correlation between ddPCR and qPCR with increased sensitivity of the ddPCR assay. Further work will be needed to determine whether multiplex ddPCR can be useful to determine PML risk in natalizumab-treated MS patients.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla , DNA Viral/genética , Humanos , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Natalizumab/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral
9.
Viruses ; 14(6)2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35746603

RESUMO

JC polyomavirus (JCPyV) is a small non-enveloped virus that establishes lifelong, persistent infection in most of the adult population. Immune-competent patients are generally asymptomatic, but immune-compromised and immune-suppressed patients are at risk for the neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Studies with purified JCPyV found it undergoes receptor-dependent infectious entry requiring both lactoseries tetrasaccharide C (LSTc) attachment and 5-hydroxytryptamine type 2 entry receptors. Subsequent work discovered the major targets of JCPyV infection in the central nervous system (oligodendrocytes and astrocytes) do not express the required attachment receptor at detectable levels, virus could not bind these cells in tissue sections, and viral quasi-species harboring recurrent mutations in the binding pocket for attachment. While several research groups found evidence JCPyV can use novel receptors for infection, it was also discovered that extracellular vesicles (EVs) can mediate receptor independent JCPyV infection. Recent work also found JCPyV associated EVs include both exosomes and secretory autophagosomes. EVs effectively present a means of immune evasion and increased tissue tropism that complicates viral studies and anti-viral therapeutics. This review focuses on JCPyV infection mechanisms and EV associated and outlines key areas of study necessary to understand the interplay between virus and extracellular vesicles.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Doenças Neurodegenerativas , Infecções por Polyomavirus , Astrócitos/metabolismo , Humanos , Vírus JC/genética
10.
J Med Case Rep ; 16(1): 235, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35689244

RESUMO

BACKGROUND: Progressive multifocal leukoencephalopathy is a rare demyelinating disease that is often secondary to lytic destruction of oligodendrocytes and, to a lesser extent, to astrocytes' response to human neurotrophic John Cunningham polyomavirus. Any underlying congenital disorder of primary or secondary immunodeficiency may predispose to virus infection and possible invasion of the brain. We present the first reported case of progressive multifocal leukoencephalopathy due to a mutation in the RAC2 gene. CASE PRESENTATION: We describe the case of a 34-year-old Iranian man with recurrent infections from the age of 2 years, along with other disorders such as nephritic syndrome, factor XI deficiency, and hypogammaglobulinemia. He was treated regularly with intravenous immunoglobulin from the age of 10 years with a diagnosis of common variable immune deficiency. Genetic testing confirmed a novel homozygous mutation in the RAC2 gene in the patient. Owing to the onset of neurological symptoms a few months ago, the patient was completely avaluated, which confirmed the diagnosis of PML. Despite all efforts, the patient died shortly after progression of neurological symptoms. CONCLUSIONS: According to previous studies, progressive multifocal leukoencephalopathy has been associated with 26 cases of primary immunodeficiency. Our patient presents a new case of primary immunodeficiency with progressive multifocal leukoencephalopathy. Accurate examination of these cases can help us to gain insight into the immune response to John Cunningham virus and better treat this potentially deadly disease.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Encéfalo , Humanos , Irã (Geográfico) , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Masculino , Mutação
12.
Front Immunol ; 13: 889148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592313

RESUMO

Treating patients with cancer complicated by severe opportunistic infections is particularly challenging since classical cancer treatments, such as chemotherapy, often induce profound immune suppression and, as a result, may favor infection progression. Little is known about the potential place of immune checkpoint inhibitors in these complex situations. Here, we report a 66-year-old man who was concomitantly diagnosed with non-small cell lung cancer and progressive multifocal leukoencephalopathy. The patient was treated with anti-PD-L1 antibody atezolizumab, which allowed effective control of both lung cancer and progressive multifocal leukoencephalopathy, as demonstrated by the patient's remarkable neurologic clinical improvement, JC viral load reduction in his cerebrospinal fluid, regression of the brain lesions visualized through MRI, and the strict radiological stability of his cancer. In parallel, treatment with atezolizumab was associated with biological evidence of T-cell reinvigoration. Hence, our data suggest that immune checkpoint inhibitors may constitute a treatment option for patients with cancer complicated by severe opportunistic infections.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Neoplasias Pulmonares , Infecções Oportunistas , Idoso , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/etiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Infecções Oportunistas/tratamento farmacológico
13.
Int J Mol Sci ; 23(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35628509

RESUMO

JC polyomavirus (JCPyV) is the causative agent of the fatal, incurable, neurological disease, progressive multifocal leukoencephalopathy (PML). The virus is present in most of the adult population as a persistent, asymptotic infection in the kidneys. During immunosuppression, JCPyV reactivates and invades the central nervous system. A main predictor of disease outcome is determined by mutations within the hypervariable region of the viral genome. In patients with PML, JCPyV undergoes genetic rearrangements in the noncoding control region (NCCR). The outcome of these rearrangements influences transcription factor binding to the NCCR, orchestrating viral gene transcription. This study examines 989 NCCR sequences from patient isolates deposited in GenBank to determine the frequency of mutations based on patient isolation site and disease status. The transcription factor binding sites (TFBS) were also analyzed to understand how these rearrangements could influence viral transcription. It was determined that the number of TFBS was significantly higher in PML samples compared to non-PML samples. Additionally, TFBS that could promote JCPyV infection were more prevalent in samples isolated from the cerebrospinal fluid compared to other locations. Collectively, this research describes the extent of mutations in the NCCR that alter TFBS and how they correlate with disease outcome.


Assuntos
Genoma Viral , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Adulto , Sítios de Ligação , Aberrações Cromossômicas , Humanos , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/virologia , Fatores de Transcrição/genética
14.
Viruses ; 14(5)2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35632711

RESUMO

Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell death protein 1 (PD-1), potentially improving the anti JCV-specific response. We used pembrolizumab with combined antiretroviral treatment (cART) on a compassionate-use basis. At each administration, clinical evaluation, MRI and laboratory testing, including CD3, CD4, CD8, PD-1 markers, HIV-RNA and JCV-DNA in cerebrospinal fluid (CSF)/plasma pairs, were performed. The JCV-specific T cell response was analysed by Elispot assay. This study included five HIV patients: four male, median age 43 years (29-52), median CD4 and CD8 count 150 (15-158) and 973 (354-1250) cell/mm3, respectively; median JCV-DNA and HIV-RNA in CSF/plasma pairs 9.540/1.503 cps/mL and 2.230/619 cp/mL, respectively. Overall, patients received between two and seven doses of pembrolizumab. After treatment, we observed JCV-DNA reduction and PD-1 down-regulation both in CSF and in plasma (high in circulating CD4 and CD8 at baseline), which remained stable at low levels in all patients. Three out of five patients showed stability of clinical picture and neuroimaging, while two others died. More data are needed in order to identify predictors of response to therapy.


Assuntos
Anticorpos Monoclonais Humanizados , Infecções por HIV , Leucoencefalopatia Multifocal Progressiva , Infecções por Polyomavirus , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , DNA Viral/genética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Vírus JC , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , RNA Viral , Ativação Viral
15.
Medicina (Kaunas) ; 58(4)2022 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35454389

RESUMO

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a viral disease characterized by progressive damage or inflammation of the cerebral white matter that can be encountered in patients with multiple sclerosis (MS). There are cases of PML caused by pharmacological agents including natalizumab. Therefore, in patients treated with this drug, early identification of PML allows changes in the treatment plan, reducing the risks of morbidity and mortality. CASE PRESENTATION: We reported the case of a 57-year-old female diagnosed with relapsing-remitting MS, who presented with PML related to natalizumab. The patient presented with change in behavioral, radiological abnormalities in the left parieto-temporal lobes. We described the longitudinal course of PML, from the diagnosis until the patient's death, documenting the progressive deterioration of her cognitive functioning, supported by changes on sequential brain scans and neurophysiological data. CONCLUSION: The neuropsychological impairment documented in this case study expands the range of treatment-related complications associated with natalizumab, and provides evidence that occurrence of "atypical" cognitive deficits in MS may support the early diagnosis of PML.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/efeitos adversos
16.
J Med Virol ; 94(8): 4015-4022, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35451090

RESUMO

Progressive multifocal leukoencephalopathy (PML) is an increasingly common and rapidly fatal demyelinating infection of central nervous system caused by the highly prevalent John Cunningham (JC) virus in immunocompromised individuals belonging to all age groups and genders. Human immunodeficiency virus (HIV) is the most common predisposing factor among other immunodeficient conditions leading to reactivation and multiple neurological symptoms. It has varied findings on magnetic resonance imaging (MRI) and diagnosis is confirmed by positive JC virus in cerebrospinal fluid (CSF). We report 12 confirmed cases of PML from a single academic center. We comprehensively described clinical presentations, risk factors, CSF and neuroimaging findings, treatment and outcome for these cases of PML, a rare disease. The cases were almost equivalently distributed among young and old age groups and both genders. Positive JC virus on CSF was present in the majority of cases along with mild to severe reduction in lymphocyte counts. Significant MRI changes were present in all cases ranging from T2 hypertense signals to white matter lesions in various regions. Treatment with the reversion of immune-modulators, optimization of antiviral therapy (ART), plasmapheresis (PLEX), IVIG, Mirtazapine, oral steroids, and others was started as soon as the diagnosis was made in the majority of the cases. However, PML is a rapidly fatal illness and hence, survival was only seen in 4 cases in our study. The objective of this article is to highlight the importance of early diagnosis of PML with CSF findings and neuroimaging, early reversion of immunosuppressive medications, and careful monitoring and treatment of HIV cases with goals to reduce mortality, long-term morbidity, and deficits.


Assuntos
Infecções por HIV , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Masculino , Neuroimagem/efeitos adversos , Universidades , West Virginia
17.
Rinsho Ketsueki ; 63(3): 206-210, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35387934

RESUMO

A 58-year-old man was diagnosed with mycosis fungoides (MF) confirmed by skin biopsy for systemic erythema that appeared in 2006 and had been on psoralen plus ultraviolet A (PUVA) therapy and topical steroids. In September 2017, he had diffuse large B-cell lymphoma and received chemotherapy. Since March 2019, tumor stage MF with large cell transformation was observed, and chemotherapy containing brentuximab vedotin (BV) was performed, which yielded a remarkable response. During the preparation for allogeneic hematopoietic stem cell transplantation, bradykinesia, delayed response, and cognitive decline were observed. Head magnetic resonance imaging fluid-attenuated inversion recovery images showed hyperintensity in the deep white matter below the bilateral frontal cortex. The general cerebrospinal fluid test revealed no abnormalities and was below the sensitivity of JC virus (JCV) quantitative PCR. As progressive multifocal leukoencephalopathy (PML) was strongly suspected from clinical symptoms and radiographic signs, ultrasensitive JCV testing was performed. The test result was positive; hence, the patient was diagnosed with PML. Chemotherapy was discontinued, but his central nervous system symptoms worsened, and he died on the 135th day of illness. We considered that PML developed based on the underlying disease and immunodeficiency caused by chemotherapy such as BV.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Micose Fungoide , Neoplasias Cutâneas , Brentuximab Vedotin , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/etiologia , Imageamento por Ressonância Magnética/efeitos adversos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/complicações , Micose Fungoide/terapia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/tratamento farmacológico
18.
Arkh Patol ; 84(2): 36-43, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35417947

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating brain damage caused by infection of oligodendrocytes and astrocytes with the lytic JC virus on the background of immunosuppression. A case report of PML with a tumor-like course is presented. Morphological diagnostics revealed non-specific staining of antibodies to Ki-67, p53, IDH1, NF and Vim in the nuclei of gliocytes affected by the JC virus. Histological examination and microscopic evaluation of the changes in the brain for the diagnosis of PML is a priority. The recommended intravital biopsy does not always help in clear verification of PML due to the limited volume of tissue fragments presented for research. For the correct interpretation of changes during an intravital pathological examination and verification of PML, it is important to take material during a stereotaxic biopsy, not only from the center, but from the edges and perifocal zone of the altered tissues for the possibility of a spatial histological assessment of the pathological process.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Biópsia , Encéfalo/patologia , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/patologia , Oligodendroglia/patologia
19.
J Neurovirol ; 28(2): 335-338, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35320511

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the CNS caused by the human polyomavirus 2 (JCV). PML predominantly occurs in immunocompromised patients. To date, no specific antiviral treatment exists, leaving only restoration of the immune system as possible treatment. In 2019, the monoclonal antibody pembrolizumab was reported as a potential treatment option in PML in a case series. Following case reports could not thoroughly confirm a positive outcome. Pembrolizumab targets the inhibitory programmed cell death protein 1 (PD-1) receptor on lymphocytes and is associated with beneficial expansion of pre-existing virus-specific T cells. Here we describe a patient with PML who benefited from combined treatment with intravenous immunoglobulins, maraviroc, and pembrolizumab.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Leucoencefalopatia Multifocal Progressiva/complicações
20.
J Neurovirol ; 28(1): 17-26, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35239145

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a frequent neurological complication in immunosuppressed patients. PML is caused by the JC virus (JCV), a neurotropic DNA polyomavirus that infects oligodendrocytes and astrocytes, causing inflammation and demyelination which lead to neurological dysfunction. The pathogenesis of PML is poorly understood due to the lack of in vitro or animal models to study mechanisms of disease as the virus most efficiently infects only human cells. We developed a human-derived brain organotypic system (also called brain organoid) to model JCV infection. The model was developed by using human-induced pluripotent stem cells (iPSC) and culturing them in 3D to generate an organotypic model containing neurons, astrocytes, and oligodendrocytes which recapitulates aspects of the environment of the human brain. We infected the brain organoids with the JCV MAD4 strain or cerebrospinal fluid of a patient with PML. The organoids were assessed for evidence of infection by qPCR, immunofluorescence, and electron microscopy at 1, 2, and 3 weeks post-exposure. JCV infection in both JCV MAD4 strain and PML CSF-exposed brain organoids was confirmed by immunocytochemical studies demonstrating viral antigens and electron microscopy showing virion particles in the nuclear compartment of oligodendrocytes and astrocytes. No evidence of neuronal infection was visualized. Infection was also demonstrated by JCV qPCR in the virus-exposed organoids and their media. In conclusion, the brain organoid model of JCV infection establishes a human model suitable for studying the mechanisms of JCV infection and pathogenesis of PML and may facilitate the exploration of therapeutic approaches.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Infecções por Polyomavirus , Animais , Encéfalo , DNA Viral/genética , Humanos , Vírus JC/genética , Organoides/patologia , Infecções por Polyomavirus/genética
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