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Специфические клеточные анализы для оценки риска PML у волчьих и множественных склерозовых пациентов с натализумбом и без него.

Прогрессивная многофукальная лейкоэнцефалопатия (PML) — оппортунистическая инфекция, вызванная вирусом JC и часто смертельная. Натальизумаб является высокоэффективной терапией для множественных склерозов (MS), но связана с высокой распространенностью PML. Нынешние метрики, используемые для стратификации пациентов, подверженных риску заболевания MS, являются неполными, в результате чего некоторые пациенты преждевременно прекращают эффективное лечение, а другие - развивают PML, несмотря на предполагаемый низкий риск. ЦЕЛЬ: Мы стремились разработать сочетание клеточных анализов с использованием п

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BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus and often fatal. Natalizumab is a highly effective therapy for multiple sclerosis (MS) but is linked to a high incidence of PML. The current metrics used to stratify MS patients at risk for PML are incomplete, leading some patients to prematurely…

Progressive multifocal leukoencephalopathy associated with sphingosine-1-phosphate receptor modulators: A large case series.

BACKGROUND: Risk factors for progressive multifocal leukoencephalopathy (PML) associated with sphingosine-1-phosphate receptor (S1PR) modula … nsidered as a potential risk factor for further validation. No conclusions could be drawn regarding JC virus serology and lymphopenia severity. CONCLUSIONS: Spontaneous adverse event reports support the observation that extended S1PR modulator exposure appears to be a robust PML risk factor. As a result, the U.S. Prescribing Information for each product i …

Chitosan-poly(ethylene oxide) nanofibrous mat as a vaginal platform for tenofovir disoproxyl fumarate - The effect of vaginal pH on drug carrier performance.

In the present work, a solution blow spun nanofibrous mat comprised of chitosan (CS) and poly(ethylene oxide) (PEO) was obtained as vaginal platform for tenofovir disoproxil fumarate (TDF) to prevent sexually transmitted infections. Apart from physicochemical and mechanical analysis, the specific steps involved studies on nanofibrous mat mucoadhesive and swelling characteristics upon pH fluctuations over the physiological range. Physicochemical analysis showed uniform drug distribution within the CS/PEO mat volume and pointed toward physical interactions between the drug and polymers. TDF-load

Leukoencephalopathy During Daratumumab-Based Therapy: A Case Series of Two Patients with Multiple Myeloma.

Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CN

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… Cerebrospinal fluid (CSF) was negative for plasma cells; lactate dehydrogenase (LDH) levels were within normal limits; and JC virus, tested via polymerase chain reaction, was not detected. … However, neither of the patients were positive for JC virus, indicating that these cases were unlikely to be related to PML. …

Infratentorial onset of progressive multifocal leukoencephalopathy in a patient with systematic lupus erythematosus complicated with lymphoma: a case report.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by reactivation of JC virus (JCV). Typical PML shows confluent, bilateral but asymmetric, subcortical lesions in the supratentorial white matter on magnetic resonance imaging (MRI). We report here a 50-year-old woman with systemic lupus erythematosus complicated with lymphoma who developed PML with atypical brain MRI findings limited to the infratentorial area at presentation. She presented with numbness on the right side of the face, including her tongue, clumsiness of the r…

Teriflunomide Inhibits JCPyV Infection and Spread in Glial Cells and Choroid Plexus Epithelial Cells.

Several classes of immunomodulators are used for treating relapsing-remitting multiple sclerosis (RRMS). Most of these disease-modifying therapies, except teriflunomide, carry the risk of progressive multifocal leukoencephalopathy (PML), a severely debilitating, often fatal virus-induced demyelinating disease. Because teriflunomide has been shown to have antiviral activity against DNA viruses, we investigated whether treatment of cells with teriflunomide inhibits infection and spread of JC polyomavirus (JCPyV), the causative agent of PML. Treatment of choroid plexus epithelial cells and astroc

The importance of mouse models to define immunovirologic determinants of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a severely debilitating and often fatal demyelinating disease of the central nervous system (CNS) in immunosuppressed individuals caused by JC polyomavirus (JCV), a ubiquitous human pathogen. Demyelination results from lytically infected oligodendrocytes, whose clearance is impaired in the setting of depressed JCV-specific T cell-mediated CNS surveillance. Although mutations in the viral capsid and genomic rearrangements in the viral non-coding region appear to set the stage for PML in the immunosuppressed population, mechanisms of demyelinat

Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS.

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab therapy in patients with multiple sclerosis (MS), which is often accompanied by an immune reconstitution inflammatory syndrome (IRIS) after removal of the drug. We describe a patient with MS who presented with simultaneous PML-IRIS 2 months after stopping natalizumab for other reasons. CASE REPORT AND RESULTS: The patient had widespread PML and severe IRIS. He received corticosteroids and displayed a vigorous JC virus-specific cellular immune response. Elevated myoinositol and lipid/creatine pe…

Immunological and clinical consequences of treating a patient with natalizumab.

BACKGROUND: Long-term therapy with natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: We prese … s. Our study may provide insights into the changes under treatment with natalizumab associated with JC virus control.

Glial cell type-specific subcellular localization of 14-3-3 zeta: an implication for JCV tropism.

14-3-3 Isoforms are shown to be upregulated or accumulated in the glial cells of autopsied patient brains affected with progressive multifocal leukoencephalopathy (PML), a demylinating disease caused by JC virus (JCV). The possible involvement of 14-3-3 in JCV tropism, however, has never been examined. To investigate a potential relationship between 14-3-3 isoforms and JCV in vitro, we examined the localization of six 14-3-3 isoforms in human neural progenitors and progenitor-derived astrocytes (PDAs) in cells without JCV exposure. The 14-3-3 zeta isoform was initially localized in the progeni…

[A case of progressive multifocal leukoencephalopathy with methionine uptake demonstrated by PET].

We report here a 55-year-old man with progressive multifocal leukoencephalopathy (PML) associated with chronic adult T cell leukemia (ATL). … strocytes. Oligodendrocytes contained nuclear inclusions which reacted with an antibody against the JC virus (JCV) antigen. These findings were consistent with those of PML. The genomic analysis of JCV from the biopsied brain revealed deletions in the regulatory region. We investigated cerebral blood flow, glucose and amino acid metabolism in this patient …

BK virus capsid antibodies are associated with protection against subsequent development of PML in HIV-infected patients.

Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus (JCPyV). Because a reciprocal relationship has been described between antibody levels to JCPyV and BK polyomavirus (BKPyV), we performed a nested case control study with pre-diagnostic serum samples from HIV infected subjects to examine the relationship between BKPyV capsid antibodies and the risk of PML. Serum samples collected 0.5-2 years before PML diagnosis from 25 cases (66 samples) and 80 matched controls (204 samples) were tested in ELISA for JCPyV, BKPyV type 1 and type 4 capsid antibodies. High levels of BKP

Fine needle aspiration biopsy of progressive multifocal leukoencephalopathy in a patient with AIDS. A case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is one of the most common opportunistic infections, with a range of 4-7% in acquired immunodeficiency syndrome (AIDS) patients. Clinical diagnosis is often difficult, and the specific pathologic agent requires cytologic and pathologic confirmation. CASE: A 38-year-old, Haitian male was admitted with a new-onset seizure disorder. On computed tomography (CT), there were right frontoparietal cortex, right external capsule and right basal ganglia lucencies. Fine needle aspiration biopsy (FNAB) of the radiolucent area revealed foci of wh

Изменение клинических и лабораторных характеристик прогрессивной многофокальной лейкоэнцефалопатии: ретроспективное национальное когертное исследование.

: Прогрессивная многофукальная лейкоэнцефалопатия (ПМЛ) является серьезной демиелинизирующей болезнью, вызванной полиомавирусом JC (JCV) и затрагивающей иммунокомпромиссированных лиц. Мы описываем демографические, клинические, радиологические и лабораторные характеристики PML и выживаемость с течением времени и в зависимости от лежащего в их основе состояния в большой ретроспективной группе пациентов. МЕТОДЫ: Это ретроспективная группа, включая итальянских пациентов ПМЛ, которые наблюдались в период с 1987 по 2024 год, с известным годом диагностики и основными заболеваниями. Результаты: Мы вкл

Сопоставим тесты на стриптиз JCVTM DxSelectTM и IMMUNOWELTM JCV в RRMS для оценки риска PML.

Риск развития прогрессивной многофукальной лейкоэнцефалопатии (ПМЛ), редкой, но потенциально смертельной оппортунистической инфекции центральной нервной системы, вызванной вирусом Дж.К. (JCV), по-прежнему является одной из главных проблем, связанных с наследственной терапией при клиническом лечении пациентов с множественным склерозом (MS). МАТЕРИАЛЫ И МЕТОДЫ: two - анализы на антитела, анализы на степию JCVTM DxSelectTM и анализы на антитела IMMUNOWELLT TM для оценки риска PML у пациентов, у которых диагностирован повторный склероз (RRMS), получивших терапию с модифицирующими заболеваниями (DM

Beyond the switch to the biosimilar of natalizumab: What is the impact of changing the JCV test?

BACKGROUND: The biosimilar drug of natalizumab was marketed with a new anti-John Cunningham virus (JCV) assay (ImmunowellTM). OBJECTIVES: To compare the performance of the ImmunowellTM JCV assay to StratifyTM, the reference one. METHODS: We analyzed retrospectively serological results from patients with multiple sclerosis (MS) followed in four French MS centers and tested simultaneously in routine with both tests. RESULTS: Two hundred and fifty-nine patients were included. Results were positive in 23.6% with StratifyTM and 61.4% with ImmunowellTM. A binary discordance was found in 37.8%. Se

John Cunningham Virus Status, Seroconversion Rate, and the Risk of Progressive Multifocal Leukoencephalopathy in Polish John Cunningham Virus-Seronegative Patients with Relapsing-Remitting Multiple Sclerosis.

INTRODUCTION: Presence of anti-JC-virus antibodies (JCVAbs) is associated with the increased risk of natalizumab (NAT)-related progressive multifocal leukoencephalopathy (PML). Little is known about seroconversion rate and time to seroconversion in relapsing-remitting multiple sclerosis (RRMS) patients treated with NAT in Poland. The aim of the study was to assess the true risk of PML, seroconversion rate, and time to seroconversion in all JCVAb-negative RRMS patients treated with NAT in Poland. METHODS: Demographic and clinical data of all Polish RRMS patients treated with NAT reimbursed by

Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry.

BACKGROUND: The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV). OBJECTIVE: To describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions. METHODS: An Italian independent collaborative repository initiative collected an

Conventional and diffusion-weighted MRI in progressive multifocal leukoencephalopathy: new elements for identification and follow-up.

PURPOSE: Progressive multifocal leukoencephalopathy (PML) is a serious disorder that primarily affects individuals with a suppressed immune system. Few semiological elements help clearly distinguish PML from other diseases included in the differential diagnosis. Moreover, the clinical course of disease may be chronic or rapidly progressive, with different magnetic resonance imaging (MRI) patterns. The purpose of this study was to confirm the diagnostic value of conventional MRI sequences combined with diffusion-weighted imaging (DWI) in PML to identify those patients with worst prognosis. MAT