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Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system (CNS) due to John Cunningham (JC) virus reactivation most often in immunocompromised patients. The brainstem and the anterior corpus callosum are uncommon locations for white matter lesions. We present a case of PML in a 40-year-old female presenting to the emergency department for a tonic seizure with transient postictal confusion. The inpatient workup revealed low cluster of differentiation cell counts (CD3 and CD4), transaminitis, positive drug screen, and abnormal electroencephalogram (EEG). The computed tomogram (CT) of the head and magnetic resonance image (MRI or MR) of the brain showed evidence of subcortical and periventricular white matter lesions in the right hemisphere extending into the brainstem and the left frontal lobe. The hospital course consisted of supportive measures, seizure treatment along with prophylaxis, and human immunodeficiency virus (HIV) management along with prophylactic antibiotics. The patient was discharged with appropriate medications and outpatient referrals. Overall, this case describes some key points. It highlights particular imaging characteristics of PML in the setting of inadequately treated HIV. For example, white matter lesions cross the anterior corpus callosum rather than the splenium, as in the "barbell" sign. In addition, the lesions extend inferiorly along the ipsilateral corticospinal tract into the midbrain and pons. This could be one of the first cases to capture both of these features given the rarity of their concomitant occurrence.
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Postoperative JC viruria is common in kidney transplant recipients, however there remains a dearth of research on perioperative JCV infection in this population. The clinical significance of JCV monitoring in kidney transplant recipients remains unclear. Based on JCV urine monitoring during the perioperative phase, renal transplant recipients who underwent perioperative and postoperative monitoring at our center were categorized into two groups: the perioperative JC virus infection group and the control group consisting of recipients without detectable JCV DNA in plasma or urine during the two-year follow-up period. A comparative analysis of baseline data was initially performed, followed by a 1:1 propensity score matching of 80 cases from each group. Within the first month after transplantation, the JC viruria group exhibited a significant decrease in the incidence of delayed graft function compared to the control group (P = 0.031).Over the two-year postoperative period, the JC viruria group displayed a significantly lower rate of acute rejection (P = 0.027). Notably, the JC viruria group demonstrated higher estimated glomerular filtration rate levels compared to the control group, particularly within the first year post-transplantation. Moreover, recipient and transplant kidney survival rates did not significantly differ between the two groups (P = 0.642). Perioperative JC viruria in kidney transplant recipients may persist beyond the initial two postoperative years. The presence of JCV is associated with lower rates of DGF and acute rejection, indicating a favorable post-transplant recovery. These findings provide novel insights into the importance of postoperative JCV monitoring.
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Virus JC , Trasplante de Riñón , Infecciones por Polyomavirus , Trasplante de Riñón/efectos adversos , Humanos , Virus JC/aislamiento & purificación , Masculino , Femenino , Persona de Mediana Edad , Infecciones por Polyomavirus/orina , Infecciones por Polyomavirus/virología , Pronóstico , Adulto , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Infecciones Tumorales por Virus/orina , Estudios Retrospectivos , Funcionamiento Retardado del Injerto , Supervivencia de InjertoRESUMEN
Progressive Multifocal Leukoencephalopathy (PML), primarily affecting immunocompromised individuals due to the John Cunningham virus (JC), is common in HIV-positive adults but rare in paediatrics. We present a unique case of a 14-year-old female with PML as the initial manifestation of HIV, with MRI lesions isolated to the posterior fossa. Initial symptoms included fever and rash, progressing to neurological deficits and ataxia. Severe immune suppression due to HIV and JC virus in the cerebrospinal fluid were confirmed. Management included immune reconstitution therapy (antiretroviral treatment) and supportive care. Despite interventions, the patient had a slow recovery with significant residual neurological sequelae. Timely recognition of Immune Reconstitution Inflammatory Syndrome (IRIS) and steroid initiation proved helpful. Antiretroviral therapy improved the survival rate of HIV-related PML, but long-term neurological sequelae, especially in posterior fossa cases, significantly impact the patient's quality of life. This case highlights diagnostic and treatment challenges in paediatric PML, particularly with atypical lesions location.
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Progressive multifocal leukoencephalopathy (PML) is a severe, demyelinating disease of the central nervous system caused by JC virus infection. The disease can be seen in sarcoidosis patients without additional risk factors. Here, we present an individual with PML secondary to sarcoidosis treated with 8 doses of pembrolizumab, a Programmed Cell-Death-1 (PD-1) Immune Checkpoint Inhibitor who showed significant improvement. This report illustrates the objective clinical and radiological improvement in a patient with PML due to sarcoidosis, and suggests further study of immune checkpoint inhibitors as a potential treatment for sarcoidosis patients with PML.
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Introduction: Progressive Multifocal Leukoencephalopathy (PML) is a rare and deadly demyelinating disease caused by JC virus (JCV) replication in the central nervous system. PML occurs exclusively in patients with severe underlying immune deficiencies, including AIDS and hematological malignancies. PML has also emerged as a significant threat to patients on potent new immunosuppressive biologics, including natalizumab in multiple sclerosis. Methods: Here, we developed an IFN-γ release assay (IGRA) that mainly detects JCV-specific effector memory T cells and effectors T cells in the blood. Results: This assay was frequently positive in patients with active PML (with a positive JCV PCR in CSF) of various underlying immunosuppression causes (84% sensitivity). Only 3% of healthy donors had a positive response (97% specificity). The frequency of positivity also increased in multiple sclerosis patients according to the time on natalizumab (up to 36% in patients treated for more than 48 months, who are considered at a higher risk of PML). Discussion: The results show this assay's frequent or increased positivity in patients with PML or an increased risk of PML, respectively. The assay may help to stratify the risk of PML.
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Interferón gamma , Virus JC , Leucoencefalopatía Multifocal Progresiva , Células T de Memoria , Humanos , Leucoencefalopatía Multifocal Progresiva/inmunología , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/etiología , Masculino , Virus JC/inmunología , Femenino , Persona de Mediana Edad , Adulto , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Natalizumab/uso terapéutico , Anciano , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/tratamiento farmacológicoAsunto(s)
Síndrome de Inmunodeficiencia Adquirida , Leucoencefalopatía Multifocal Progresiva , Humanos , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Masculino , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Huésped Inmunocomprometido , Imagen por Resonancia Magnética , Diagnóstico Diferencial , Virus JC/aislamiento & purificación , Adulto , Infecciones Oportunistas Relacionadas con el SIDA/diagnósticoRESUMEN
BACKGROUND: Several studies have reported the presence of JC virus (JCV) in human tumors, The association of JCV and CRC remains controversial. This study aimed to evaluate the rearranged NCCR region of the detected JCV DNA in CRC patients' tissue samples. METHODS: In this case-control study, tumor tissues (n = 60), adjacent normal tissues (n = 60), and urine samples (n = 60) of the CRC patients were collected. The nested PCR was employed to detect the VP1 and NCCR regions of the JCV genome. The positive JCV PCR products were sequenced and a phylogenetic tree was constructed to determine the JCV genotypes. After extracting RNA and preparing cDNA, the expression of JCV LTAg was examined in 60 tumor tissues and 60 adjacent normal tissues. The analysis of JCV LTAg expression was performed using GraphPad Prism software version 8. RESULTS: The analysis reveals that JCV DNA was detected in 35/60 (58.3%) tumor tissues, while 36/60 (60.0%) of adjacent normal tissues (p = 0.85). JCV DNA was detected in 42/60 (70.0%) urine samples when compared to 35/60 (58.3%) tumor tissues of CRC patients and was not found significant (P = 0.25). The phylogenetic tree analysis showed the dominant JCV genotype 3, followed by genotype 2D was distributed in tumor tissue, normal tissue, and urine samples of the CRC patients. Analysis of randomly selected NCCR sequences from JCV regions in tumor tissue samples revealed the presence of rearranged NCCR blocks of different lengths.: 431 bp, 292 bp, 449 bp, and 356 bp. These rearranged NCCR blocks differ from the rearranged NCCR blocks described in PML-type Mad-1, Mad-4, Mad-7, and Mad-8 prototypes. The expression of JCV LTAg was significantly different in tumor tissue compared to normal tissue, with a p-value of less than 0.002. CONCLUSION: A significant proportion of 35%> of the tumor tissue and urine samples of the CRC patients was found to be positive for JCV DNA (P = 0.25). The parallel analysis of tumor and urine samples for JCV DNA further supports the potential for non-invasive screening tools. This study provides new insights into Rearranged NCCR variant isolates from patients with CRC. The significant difference in JCV LTAg expression between tumor and normal tissue indicates a latent JCV status potentially leading to cancer development.
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Neoplasias Colorrectales , ADN Viral , Virus JC , Filogenia , Humanos , Virus JC/genética , Virus JC/aislamiento & purificación , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Colorrectales/virología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/orina , ADN Viral/orina , ADN Viral/genética , Estudios de Casos y Controles , Anciano , Adulto , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/orina , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/orina , Reordenamiento Génico , Genotipo , Anciano de 80 o más AñosRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a rare, demyelinating infectious disease of the central nervous system, primarily affecting immunosuppressed individuals, such as those with acquired immunodeficiency syndrome (AIDS) or undergoing immunosuppressive therapy. The causative agent is the dormant John Cunningham (JC) polyomavirus, which reactivates in immunocompromised patients. PML is diagnosed through clinical observations, imaging, and polymerase chain reaction (PCR) analysis, detecting JC virus deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF). Here, we report a case of a 42-year-old male, recently diagnosed with human immunodeficiency virus (HIV), who presented with slurred speech, difficulty articulating, tingling in both feet, difficulty walking, and significant weight loss. Examination revealed absent reflexes, coordination impairment, and diminished vibration sense. Blood tests showed anemia, elevated D-dimer, and HIV-1 positivity with a low CD4 count. CSF analysis indicated a lymphocytic profile with elevated protein and marginally increased adenosine deaminase (ADA). Autoantibody testing was positive for antinuclear antibodies (ANA), but CSF culture and India ink staining were negative. Magnetic resonance imaging (MRI) of the brain revealed hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the left peritrigonal and parietal white matter, suggesting demyelination. The diagnosis of PML was confirmed by a positive JC virus PCR result from the CSF. The patient was started on combination antiretroviral therapy (cART) and supportive measures to improve immune status. This case underscores the importance of considering PML in patients with new-onset neurological symptoms and immunosuppression.
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BACKGROUND: Epidemiological studies on predisposing conditions and outcomes of progressive multifocal leukoencephalopathy (PML) cases have been carried out exclusively in high-income countries. We aim to report and compare the main characteristics and outcomes of patients with PML and several underlying diseases in a referral center in a middle-income country. METHODS: We performed a retrospective cohort study of PML cases admitted to a tertiary care hospital in São Paulo, Brazil during 2000-2022. Demographic and PML-specific variables were recorded. One-year case-fatality rate and factors associated with death were identified using a multivariate Cox proportional hazards regression model. RESULTS: Ninety-nine patients with PML were included. HIV infection (84.8%) and malignancy (14.1%) were the most prevalent underlying conditions. Other predisposing diseases were autoimmune/inflammatory diseases (5.1%) and solid organ transplantation (1.0%). One (1.0%) patient had liver cirrhosis and another (1.0%) patient was previously healthy. Focal motor deficits (64.2%) and gait instability (55.1%) were the most common signs. The one-year case-fatality rate was 52.5% (95% CI 42.2-62.7). The one-year case-fatality rate (95% CI) in patients with or without malignancy (85.7%, 95% CI 57.2-98.2% and 47.1%, 95% CI 36.1-58.2%, respectively) were statistically different (P = 0.009). Crude and adjusted Cox regression models identified malignancy as independently associated with death (adjusted HR = 3.92, 95% CI 1.76-8.73, P = 0.001). CONCLUSIONS: HIV/AIDS was the predisposing condition in 84.8% of PML cases. The one-year case-fatality rate was 52.5% and having a malignancy was independently associated with death. This study reports emerging data on the epidemiology and outcome of PML in a middle-income country.
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Solid organ transplant recipients require ongoing immunosuppression to prevent acute rejection, which puts them at risk of opportunistic infections. Viral infections are particularly challenging to prevent and treat as many establish latency and thus cannot be eliminated, whereas targets for small molecule antiviral medications are limited. Resistance to antivirals and unacceptable toxicity also complicate treatment. Virus-specific T cell therapies aim to restore host-specific immunity to opportunistic viruses that is lacking due to ongoing immunosuppressive therapy. This minireview will provide a state-of-the-art update of the current virus-specific T cell pipeline and translational research that is likely to lead to further treatment options for viral infections in solid organ transplant recipients.
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Trasplante de Órganos , Linfocitos T , Receptores de Trasplantes , Virosis , Humanos , Trasplante de Órganos/efectos adversos , Virosis/inmunología , Virosis/etiología , Virosis/terapia , Linfocitos T/inmunología , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología , Rechazo de Injerto/inmunologíaRESUMEN
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.
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Virus BK , Genotipo , Virus JC , Trasplante de Riñón , Epidemiología Molecular , Infecciones por Polyomavirus , Humanos , Virus BK/genética , Virus BK/aislamiento & purificación , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/orina , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Virus JC/genética , Virus JC/aislamiento & purificación , Estudios de Casos y Controles , Adulto , Esparcimiento de Virus , Anciano , Receptores de Trasplantes/estadística & datos numéricos , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/orina , ADN Viral/orina , ADN Viral/genética , Aloinjertos/virologíaRESUMEN
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus predominantly affecting immunocompromised individuals. Nowadays, HIV, hematological malignancies and iatrogenic immune suppression account for most PML cases. For unknown reasons, spinal cord is classically protected from PML lesions. Here, we report the course of a patient harboring spinal cord lesions in the context of PML with immune reconstitution inflammatory syndrome and review the eight other cases reported in the literature so far. Then, we discuss the evolving spectrum of PML over recent years, potentially making its diagnosis more challenging.
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Síndrome Inflamatorio de Reconstitución Inmune , Virus JC , Leucoencefalopatía Multifocal Progresiva , Médula Espinal , Humanos , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/inmunología , Síndrome Inflamatorio de Reconstitución Inmune/virología , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/patología , Virus JC/inmunología , Virus JC/patogenicidad , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/inmunología , Leucoencefalopatía Multifocal Progresiva/patología , Leucoencefalopatía Multifocal Progresiva/virología , Imagen por Resonancia Magnética , Médula Espinal/patología , Médula Espinal/virología , Médula Espinal/diagnóstico por imagen , Médula Espinal/inmunologíaRESUMEN
The strategy for progressive multifocal leukoencephalopathy (PML) in solid organ transplant recipients primarily focuses on reducing immunosuppressive therapy. However, this approach offers limited efficacy and carries a high risk of graft loss. Here, we present the case of a 64-year-old male kidney transplant recipient with a high degree of immunosuppression who developed PML in October 2022. Despite the standard reduction of immunosuppressive therapy, the patient's condition continued to deteriorate, as evidenced by worsening neurological symptoms and increasing JC virus (JCV) DNA levels in cerebrospinal fluid. This prompted the innovative use of BKPyV-virus-specific T cell (BKPyV-VST) therapy, given the genetic similarities between BK and JCVs. Infusion of third-party donor BKPyV-VST resulted in clinical stabilization, a significant reduction in JCV-DNA levels, and the emergence of a JCV-specific T cell response, as observed in enzyme-linked immunospot assays and TCRß sequencing. This represents the first case report of successful third-party BKPyV-VST therapy in a kidney recipient presenting PML, without graft-versus-host disease or graft dysfunction.
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Virus BK , Trasplante de Riñón , Leucoencefalopatía Multifocal Progresiva , Infecciones por Polyomavirus , Linfocitos T , Humanos , Leucoencefalopatía Multifocal Progresiva/terapia , Leucoencefalopatía Multifocal Progresiva/inmunología , Leucoencefalopatía Multifocal Progresiva/etiología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Linfocitos T/inmunología , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/terapia , Pronóstico , Virus JC/inmunología , Receptores de Trasplantes , Tratamiento Basado en Trasplante de Células y Tejidos/métodosRESUMEN
BACKGROUND: Natalizumab (NAT) pharmacokinetics and pharmacodynamics are complicated by arm exchange with endogenous IgG4, resulting in a mixture of a more potent intact, bivalent form and a less potent, functionally monovalent form. Total NAT and endogenous IgG4 concentrations vary considerably across patients. This study assessed the concentration of intact NAT, and how it relates to total NAT and endogenous IgG4 levels in blood and saliva. METHODS: Paired serum and saliva samples from a small cohort of relapsing-remitting multiple sclerosis patients were measured for levels of intact NAT, total NAT, IgG and IgG4. RESULTS: Intact NAT concentration was dependent on both total NAT and endogenous IgG4 levels. Low endogenous IgG4 led to a higher ratio of intact NAT to total NAT, while the opposite was observed in subjects with high endogenous IgG4. Serum and saliva measurements show good concordance. CONCLUSIONS: Intact NAT concentration is influenced by both NAT pharmacokinetics and endogenous IgG4 levels. Patients with low IgG4 levels can have high concentrations of intact NAT even with lower levels of total NAT, which may explain cases of NAT-associated progressive multifocal leukoencephalopathy (PML) in such patients. Monitoring both forms of NAT could better guide dosing, maximizing drug efficacy and safety.
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Inmunoglobulina G , Factores Inmunológicos , Esclerosis Múltiple Recurrente-Remitente , Natalizumab , Saliva , Humanos , Natalizumab/farmacocinética , Natalizumab/administración & dosificación , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/inmunología , Inmunoglobulina G/sangre , Femenino , Masculino , Adulto , Factores Inmunológicos/farmacocinética , Factores Inmunológicos/administración & dosificación , Saliva/química , Persona de Mediana EdadRESUMEN
The John Cunningham virus (JCV) is a polyomavirus that usually infects people at a young age and does not cause any symptoms in immunocompetent individuals. However, in immunocompromised individuals, such as kidney transplant recipients, JCV can cause severe and potentially fatal disease. Unfortunately, JCV has not been researched as extensively as the BK virus and is not mentioned in relevant kidney transplant guidelines. This lack of attention to JCV can lead to less consideration in kidney transplant patients' care. Surveillance using locally available diagnostic methods is of the utmost importance. The presence of JCV can be diagnosed with urine decoy cells, viruria, or viremia verified by the PCR method. A low threshold for considering JCV as a possible cause of any neurological or renal dysfunction in kidney transplant recipients must be maintained. In such cases, kidney and brain biopsy are indicated. Maintaining the appropriate immunosuppression while avoiding over-immunosuppression to prevent JCV disease is crucial, and the approach should be individual, according to overall immunological risk. We hypothesize that the presence of the JCV can indicate overt immunosuppression and identify kidney transplant recipients more prone to opportunistic infections and diseases, including some malignancies. To explore that, future observational studies are needed.
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Progressive multifocal leukoencephalopathy (PML) is a rare and fatal demyelinating disease of the central nervous system (CNS). The case we describe highlights the importance of considering a diagnosis of PML early (<1 year) after lung transplant.
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Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML.
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Virus JC , Leucoencefalopatía Multifocal Progresiva , Lupus Eritematoso Sistémico , Imagen por Resonancia Magnética , Humanos , Leucoencefalopatía Multifocal Progresiva/diagnóstico por imagen , Leucoencefalopatía Multifocal Progresiva/líquido cefalorraquídeo , Leucoencefalopatía Multifocal Progresiva/virología , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/patología , Virus JC/genética , Virus JC/patogenicidad , Femenino , Persona de Mediana Edad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/líquido cefalorraquídeo , Lupus Eritematoso Sistémico/diagnóstico por imagen , Lupus Eritematoso Sistémico/virología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Linfopenia/virología , Linfopenia/diagnóstico por imagen , Linfopenia/complicaciones , Linfopenia/líquido cefalorraquídeo , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/virología , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , ADN Viral/líquido cefalorraquídeo , ADN Viral/genética , Linfocitos/patología , Linfocitos/inmunología , Linfocitos/virología , Azatioprina/uso terapéutico , Azatioprina/efectos adversosRESUMEN
A patient undergoing cord blood transplantation for refractory angioimmunoblastic T-cell lymphoma was subsequently managed with long-term immunosuppressants for chronic graft-versus-host disease (GVHD). On day 591 post-transplant, she exhibited disorientation and cognitive dysfunction. Magnetic resonance imaging (MRI) of the brain revealed two hyperintense foci in the white matter, suggestive of progressive multifocal leukoencephalopathy (PML). However, we did not include PML in the differential diagnosis at that time. Unfortunately, she developed progressive cognitive impairment, and repeated brain MRIs showed a progression in lesion size. She was still taking immunosuppressants to control her GVHD, therefore we suspected PML. The diagnosis of PML was confirmed through the detection of a John Cunningham (JC) virus in the cerebrospinal fluid on day 640 post-transplant. This report highlights the critical need to consider PML in differential diagnoses for post-allogeneic transplant patients, especially those who exhibit progressive neurological symptoms while on prolonged immunosuppressant therapy.
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Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Inmunosupresores , Leucoencefalopatía Multifocal Progresiva , Imagen por Resonancia Magnética , Humanos , Leucoencefalopatía Multifocal Progresiva/etiología , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/líquido cefalorraquídeo , Femenino , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Linfoma de Células T/terapia , Virus JC/aislamiento & purificación , Diagnóstico Diferencial , Persona de Mediana Edad , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus.
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Virus JC , Vacunas , Humanos , Epítopos/genética , Simulación del Acoplamiento Molecular , Escherichia coli , Vacunología , Vacunas de Subunidad/genética , Epítopos de Linfocito T/genética , Biología Computacional , Epítopos de Linfocito B , Simulación de Dinámica MolecularRESUMEN
An 84-year-old Japanese woman presented with left hemiplegia 8 months after completing chemotherapy for mantle cell lymphoma. Brain magnetic resonance imaging (MRI) revealed a hyperintense lesion extending from the right parietal lobe to the left parietal lobe. Compared with these MRI results, 18F-THK5351 PET revealed more extensive accumulation. A brain biopsy showed progressive multifocal leukoencephalopathy (PML). Immunohistochemistry and John Cunningham virus (JCV) DNA-polymerase chain reaction indicated JCV infection. Therefore, a diagnosis of PML was made. 18F-THK5351 PET, indicative of activated astrocytes, clearly depicted PML lesions composed of reactive and atypical astrocytes. 18F-THK5351 PET may capture fresh progressive PML lesions better than MRI.