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The HHV6 paradox: ubiquitous commensal or insidious pathogen? A two-step in situ PCR approach.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) and multiple sclerosis (MS) are demyelinative diseases of the central nervous system (CNS). PML occurs mostly in individuals with AIDS-impaired immunity and is thought to be caused by JC polyoma virus (JCV). In MS a neurotrophic virus trigger is suspected, but the precise etiology remains unknown. Human herpesvirus 6 (HHV6) is a ubiquitous, commensal and usually benign beta-herpesvirus. Some researchers have found evidence for HHV6 infection in MS plaques and sera. We recently demonstrated a high frequency of cells containing HHV6 ge

Search for virus nucleic acid sequences in postmortem human brain tissue using in situ hybridization technology with cloned probes: some solutions and results on progressive multifocal leukoencephalopathy and subacute sclerosing panencephalitis tissue.

In order to obtain a useful and readily applicable in situ hybridization (ISH) protocol for progressive central nervous system (CNS) disease … ed with PML and one patient who died from SSPE were studied using ISH with a tritium-labeled cloned JC virus DNA probe and a measles-cloned nucleocapsid (NC) gene cDNA probe, respectively. This report constitutes a methodological framework as well as a detailed neuropathological analysis of identified brain cell populations within which in situ hybridizati …

Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner.

UNLABELLED: Mouse polyomavirus (MPyV) is a ubiquitous persistent natural mouse pathogen. A glutamic acid (E)-to-glycine (G) difference at po … sid-mediated tropism properties of the MPyV strain. IMPORTANCE: Isolates of the human polyomavirus JC virus from patients with the frequently fatal demyelinating brain disease progressive multifocal leukoencephalopathy (PML) carry single amino acid substitutions in the domain of the VP1 capsid protein that binds the sialic acid moiety of glycoprotein/glyc …

Immunosuppression increases JC polyomavirus large T antigen DNA load in the brains of patients without progressive multifocal leukoencephalopathy.

The relationship between latent JC polyomavirus (JCV) infection and progressive multifocal leukoencephalopathy (PML) remains unclear. In this study, JCV DNA was quantified by real-time polymerase chain reaction (qPCR) in brain and kidney tissue from patients without PML. Immunosuppressed patients had significantly higher JCV DNA levels in brain, compared with immunocompetent patients (P = .001). An inverse relationship was observed between CD4(+) T-cell counts and qPCR-determined brain JCV load among patients with HIV infection (r(2) = -0.9; P = .01; n = 7). Higher kidney JCV DNA load was stro

Alteration in the JC polyomavirus genome is enhanced in immunosuppressed renal transplant patients.

JC polyomavirus (JCV) DNAs derived from urine generally contain an archetypal regulatory sequence, whereas regulatory regions of JCVs in the brain with progressive multifocal leukoencephalopathy (PML) have specifically altered regulatory regions. However, JCV DNAs with regulatory regions that deviate from the archetype sometimes occur in the urine of non-PML patients. In this study, we compared the incidence of these rearranged regulatory regions between immunosuppressed (renal transplant recipients) and nonimmunosuppressed patients. We found that the incidence of rearranged JCV regulatory reg

JCPyV NCCR analysis in PML patients with different risk factors: exploring common rearrangements as essential changes for neuropathogenesis.

BACKGROUND: During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms:

Преобразование и реверсия анти-Джон Каннингемского вируса серостатуса: перспективное исследование.

ВВЕДЕНИЕ: Определение антител против вируса Джона Каннингема (JCV) является важным инструментом для стратификации риска у пациентов с множественным склерозом (MS), прошедших лечение натальизумаба. Для выявления изменений в серостатусе предлагается проводить шестимесячные тесты на негатив антитела против JCV и пациентов с низким индексом антител. Мы провели перспективное исследование с предопределёнными интервалами тестирования, с тем чтобы изучить предсказуемость состояния антиорганических антиДК и интервалы для повторных испытаний. В нашем исследовании приняли участие 109 пациентов клиники MS

Progressive Multifocal Leukoencephalopathy in a Kidney Transplant Recipient.

Progressive multifocal leukoencephalopathy (PML) is a debilitating and often fatal viral disease of the central nervous system. A 39-year-old male kidney transplant recipient presented to our hospital with weakness of the left arm and leg, his immunosuppressive regimen consisted of tacrolimus, mycophenolate sodium, and meprednisone. Magnetic resonance imaging of the brain revealed hypercellularity in neural tissue and a lesion affecting the right ventral and lateral areas of the thalamus and the posterior limb of the internal capsule. The cerebrospinal fluid tested negative for bacteria, fungi

Good outcome of brain stem progressive multifocal leukoencephalopathy in an immunosuppressed renal transplant patient: Importance of early detection and rapid immune reconstitution.

Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remis

Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies.

BACKGROUND: Previous estimates of risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis receiving natalizumab were stratified by three risk factors: anti-John Cunningham virus (JCV) antibodies in serum, previous immunosuppressant use, and treatment duration, which were estimated using population-based assumptions. We aimed to calculate PML risk estimates from patient-level risk-factor data and to stratify risk by concentrations of anti-JCV antibody in serum (anti-JCV antibody index). METHODS: Data on natalizumab-treated patients were pooled from four lar

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients.

Natalizumab is currently one of the best options for treatment of patients with Multiple Sclerosis who have failed traditional prior therapies. However, prolonged use, prior immunosuppressive therapy and anti-JCV antibody status have been associated with increased risk of developing progressive multifocal leukoencephalopathy (PML). The evaluation of these conditions has been used to estimate risks of PML in these patients, and distinct (sometimes extreme) approaches are used to avoid the PML onset. At this time, the biggest issue facing the use of Natalizumab is how to get a balance between th

Progressive multifocal leukoencephalopathy with gastrointestinal disease in a pediatric kidney transplant recipient.

PML is a demyelinating disease of the central nervous system caused by infection with JCV. Several cases of PML in bone marrow and solid organ transplant recipients have been reported in recent years. JCV has been isolated from the gastrointestinal mucosa of immunocompromised patients, but there are no published reports of PML associated with symptomatic gastrointestinal involvement in kidney transplant recipients. We report a case of a nine-yr-old girl with a kidney transplant who developed a severe gastrointestinal illness causing pseudo-obstruction in association with PML. JCV was suspected

Progressive multifocal leukoencephalopathy developing in advanced pulmonal sarcoidosis.

Coincidence of pulmonal sarcoidosis and progressive multifocal leukoencephalopathy (PML) rarely occurs. So far an entire course has been recorded in only very few cases. We demonstrate the case of a 49-year-old male developing an infratentorial localized PML in the setting of advanced pulmonal sarcoidosis. PML was not included in the diagnostic considerations in the first instance. Regarding the diagnosis of pulmonal sarcoidosis proved by lung biopsy, the neurological impairment was first thought to be due to a neurosarcoidosis. But magnetic resonance tomography (MRI) clearly showed a demyelin

Beyond Bacteria: The Emerging Role of the Gut Virome and Mycobiome in Celiac Disease.

Background/Objectives: Celiac disease (CeD) is a complex autoimmune enteropathy triggered by gluten intake in genetically predisposed individuals. While the bacterial microbiome has been extensively studied in CeD, the role of the gut virome and mycobiome is less well defined. Emerging evidence suggests that viruses and fungi may influence mucosal immunity, intestinal permeability and gluten tolerance, acting as potential environmental cofactors in the onset of this disease. Methods: A narrative review of the literature was conducted to summarize current knowledge of the composition, developme

Серологический скрининг и обновление вакцин в группе пациентов с множественным склерозом в качестве стратегии предотвращения возобновления инфекции во время иммунодепрессантной терапии.

ВВЕДЕНИЕ: Серологическое обследование и вакцинация играют решающую роль в предотвращении инфекционных осложнений у пациентов с множественным склерозом (МС). Стандартизация тестов и протоколов вакцинации имеет важное значение для пациентов, проходящих курс лечения. ЦЕЛЬ: Данное исследование было направлено на оценку подверженности инфекционным заболеваниям путем проведения серологических тестов и обновления вакцин для пациентов, страдающих MS. МЕТОДЫ: В период с февраля 2021 года по июнь 2023 года неврологическая служба Метрополитического университета Сантоса провела перекрестное исследование п

Совпадение в аннотации оригинала
INTRODUCTION: Serological screening and vaccination play a crucial role in preventing infectious complications in patients with Multiple Scl … umab and cladribine (Cladribine) and corticoid for MS flare-ups. Seroprevalence was: 66.0 % for the JC virus, 61.4 % Toxoplasmosis, 50.9 % Mononucleosis, 84.5 % Cytomegalovirus, 85.4 % Measles, 72.2 % Mumps, 92.6 % Rubella, and 94.2 % Varicella. No cases of HIV, HCV, HBV, HTLV or syphilis were detected. Vaccine cover was: 75 % influenza, 68.7 % Hepatitis B …

Epidemiology of progressive multifocal leukoencephalopathy in Japan and effectiveness of mefloquine: A retrospective analysis of a nationwide inpatient database.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is an infrequent yet devastating neurological infection that arises in immunocompromised patients. The epidemiological features of PML in Japan and its evolution in recent years remain unclear. There are no established treatments that directly target PML. Although mefloquine has shown in vitro activity against JC virus, its clinical effectiveness has not been confirmed in population-level studies. METHODS: We retrospectively analyzed the admission data of patients with PML recorded in the Diagnosis Procedure Combination (DPC) data…

Risk of natalizumab-associated PML in patients with MS is reduced with extended interval dosing.

OBJECTIVE: To use the large dataset from the Tysabri Outreach: Unified Commitment to Health (TOUCH) program to compare progressive multifocal leukoencephalopathy (PML) risk with natalizumab extended interval dosing (EID) vs standard interval dosing (SID) in patients with multiple sclerosis (MS). METHODS: This retrospective cohort study included anti-JC virus antibody-positive patients (n = 35,521) in the TOUCH database as of June 1, 2017. The effect of EID on PML risk was evaluated with 3 planned analyses using Kaplan-Meier methods stratified by prior immunosuppressant use. Risk of PML was an…

Incidence and prognosis of immune reconstitution inflammatory syndrome in HIV-associated progressive multifocal leucoencephalopathy.

BACKGROUND AND PURPOSE: Progressive multifocal leucoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-IRIS) is the paradoxical worsening or unmasking of preexisting infection with JC virus attributable to a rapid recovery of the immune system after highly active antiretroviral therapy (HAART) initiation. We investigated the incidence and factors associated with PML-IRIS in HIV-infected patients. We also studied its influence on mortality of PML and the effect of corticosteroid therapy. METHODS: Single-center retrospective analysis of HIV-infected patients diagnosed wi…

Hyperintense cortical signal on magnetic resonance imaging reflects focal leukocortical encephalitis and seizure risk in progressive multifocal leukoencephalopathy.

OBJECTIVE: To determine the frequency of hyperintense cortical signal (HCS) on T1-weighted precontrast magnetic resonance (MR) images in progressive multifocal leukoencephalopathy (PML) patients, its association with seizure risk and immune reconstitution inflammatory syndrome (IRIS), and its pathologic correlate. METHODS: We reviewed clinical data including seizure history, presence of IRIS, and MR imaging scans from PML patients evaluated at our institution between 2003 and 2012. Cases that were diagnosed either using cerebrospinal fluid JC virus (JCV) polymerase chain reaction, brain biops…

Outcome and survival of asymptomatic PML in natalizumab-treated MS patients.

OBJECTIVE: As of 3 September 2013, 399 cases of natalizumab-associated progressive multifocal leukoencephalopathy (PML) were confirmed in multiple sclerosis (MS) patients. We evaluated outcomes of natalizumab-treated MS patients who were asymptomatic at PML diagnosis. METHODS: Analyses included data available as of 5 June 2013. Asymptomatic patients diagnosed with PML by magnetic resonance imaging (MRI) findings and JC virus DNA detection in the central nervous system were compared with patients presenting with symptoms at diagnosis. Demographics, MRI, and survival over 12 months were analyze…