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Effectiveness of Immune Checkpoint Inhibitors in Transplant Recipients with Progressive Multifocal Leukoencephalopathy.

Antibodies against PD1 have been used to treat progressive multifocal leukoencephalopathy (PML), a rare brain disease caused by JC virus. We used these antibodies (nivolumab) to treat PML in 3 kidney transplant recipients. All died within 8 weeks of diagnosis. Hence, nivolumab did not improve PML outcome after solid organ transplantation.

Early years of biological agents therapy in Crohn's disease and risk of the human polyomavirus JC reactivation.

Although the remarkable efficacy of biological therapy has resulted in significant success in inflammatory bowel disease (IBD) management, susceptibility to infections remains a concern. The biological agents include the tumor necrosis factor-alpha (TNF-alpha) inhibitors, for instance infliximab, and other immunomodulating agents, such as natalizumab. Progressive multifocal leukoencephalopathy (PML), a rare but mostly fatal opportunistic brain infection caused by reactivation of the human polyomavirus JC virus (JCV), has been found in two patients with multiple sclerosis and one patient with C…

[Progressive multifocal leukoencephalopathy--epidemiology, clinical pictures, diagnosis and therapy].

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the reactivation of a ub … the treatment guidelines of patients with PML based on recent advances in the understanding of the JC virus biology.

Infection by agnoprotein-negative mutants of polyomavirus JC and SV40 results in the release of virions that are mostly deficient in DNA content.

BACKGROUND: Human polyomavirus JC (JCV) is the etiologic agent of a brain disease, known as progressive multifocal leukoencephalopathy (PML). The JCV genome encodes a small multifunctional phospho-protein, agnoprotein, from the late coding region of the virus, whose regulatory functions in viral replication cycle remain elusive. In this work, the functional role of JCV and SV40 agnoproteins in virion release was investigated using a point mutant (Pt) of each virus, where the ATG codon of agnoprotein was mutated to abrogate its expression. RESULTS: Analysis of both viral protein expression and

Progressive multifocal leukoencephalopathy and antipsoriatic drugs: assessing the risk of immunosuppressive treatments.

Progressive Multifocal Leukoencephalopathy (PML) is a rare and often fatal opportunistic demyelinating disorder secondary to central nervous system infection by the polyomavirus John Cunningham (JC), a common infecting agent in human populations, with 50-70% of healthy individuals having antibodies to the virus. Although human immunodeficiency virus (HIV) infection remains the most common predisposing factor for PML, which can occur also in association with hematologic malignant neoplasms or iatrogenic immunosuppression in the setting of organ transplantations, recently JC virus has been recog…

Lack of specific T- and B-cell clonal expansions in multiple sclerosis patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare, potentially devastating myelin-degrading disease caused by the JC virus. PML occurs preferentially in patients with compromised immune system, but has been also observed in multiple sclerosis (MS) patients treated with disease-modifying drugs. We characterized T and B cells in 5 MS patients that developed PML, 4 during natalizumab therapy and one after alemtuzumab treatment, and in treated patients who did not develop the disease. Results revealed that: i) thymic and bone marrow output was impaired in 4 out 5 patients at the time of P…

Clinicopathological study of early progressive multifocal leukoencephalopathy incidentally found in a schizophrenia patient.

A 58-year-old Japanese man developed psychomotor excitement and hallucinatory paranoia at age 53, which gradually developed to residual schi … On the other hand, the white matter was relatively intact. Immunohistochemical analysis using anti-JC virus protein, VP-1 antibody, demonstrated JC virus-infected cells in not only abnormal glial cells and neurons but also normal-looking cells, which are suggestive of progressive multifocal leukoencephalopathy (PML). Immunostaining for GFAP revealed sever …

Агнопротеин полиомавируса JC выпускается инфицированными клетками: доказательства его поглощения клетками неинфекционными соседними клетками.

Полиомавирус JC реплицируется в глиальных клетках мозга и вызывает смертельное демиелионирующее заболевание, прогрессивную многофукальную лейкоэнцефалопатию (PML). Как правило, ПМС наблюдается у пациентов с иммунокомпромиссными заболеваниями, в частности у больных СПИДом и пациентов с хроническими иммунодепрессивными режимами. Поздняя последовательность лидера вируса JC содержит открытую рамку считывания, кодирующую небольшой нормативный протеин, называемый агнопротеином. Агнопротеин вносит свой вклад в прогрессирующую вирусную инфекцию, играя значительную роль в цикле распространения вирусов.

Совпадение в аннотации оригинала
Poliomavirus JC replicates in glial cells in the brain, and causes the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). PML is usually seen in patients with underlying immunocompromised conditions, notably among AIDS patients and those on chronic immunosuppressive regimens. The late leader sequence of JC virus contains an open r…

Атезолисумаб Лечение прогрессивной многофукальной лейкоэнцефалопатии.

Atezolizumab успешно восстановила иммунитет от вируса JC у пациента в Бельгии с прогрессивной многофукальной лейкоэнцефалопатией, о чем свидетельствует клиническая, вирологическая и радиологическая реакция на лечение. Однако это лечение также привело к возникновению иммунного синдрома возрождения и опасным для жизни неблагоприятным явлениям, связанным с иммунной деятельностью. Эти заболевания были обработаны кортикостероидами, что привело к сопротивляемости лечению.

Совпадение в аннотации оригинала
Atezolizumab successfully reinvigorated JC virus immunity in a patient in Belgium with progressive multifocal leukoencephalopathy, as demonstrated by clinical, virologic, and radiologic response to treatment. However, the treatment also resulted in immune reconstitution inflammatory syndrome and life-threatening immune-related adverse events. These condition…

Progressive Multifocal Leukoencephalopathy in a Young Medication-Noncompliant HIV Patient: A Case Report and Literature Review.

Progressive multifocal leukoencephalopathy (PML) is a rare and debilitating opportunistic infection of the central nervous system (CNS) caused by the John Cunningham (JC) virus. It predominantly affects immunocompromised individuals, including those with advanced HIV infection. The incidence of PML in people living with human immunodeficiency virus (HIV) has significantly declined in the era of antiretroviral therapy (ART). We report a case of PML in a young patient with a history of medication non-compliance, presenting with progressive neurological deficits, underscoring the importance of ad

[Interactions between HIV virus and the nervous system: recent pathogenic data and hypotheses].

Disorders of the nervous system frequently complicate Acquired Immune Deficiency Syndrome (AIDS). They may be related to the development of opportunistic agents (toxoplasmosis, cryptococcossis, cytomegalovirus, JC Virus), or primary CNS lymphoma. There is also a constellation of neurologic disorders which may result from direct Human Immunodeficiency Virus (HIV) replication in the CNS and HIV has been found in brain and CSF of numerous patients suffering from AIDS. The precise cellular localization of HIV is not known, but the macrophage seems to be a strong candidate for HIV replication in CN…

Pseudovirus mimics cell entry and trafficking of the human polyomavirus JCPyV.

The normally asymptomatic human polyomavirus, JCPyV, is the causative agent of a rare but fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). Individuals at risk for developing PML include those with AIDS, with other underlying immunosuppressive diseases, and in patients treated with immunomodulatory regimens. Drugs to prevent viral reactivation in the setting of immunosuppression or immunomodulation could be used to sustain lives. Development of such drugs has been impeded by the difficulty of growing and studying the virus. We sought to develop a more effic

[Progressive multifocal leukoencephalopathy in a patient with acquired immunodeficiency syndrome].

We report a 28 year old heterosexual male with AIDS that presented with progressive motor disturbances and malaise. Light and transmission electron microscopy of a stereotaxic brain biopsy demonstrated a progressive multifocal leukoencephalopathy. This is a demyelinating infectious cerebral disease attributed to JC virus and must be considered in the differential diagnosis of central nervous system disturbances in AIDS patients.

Autopsy case of the cerebellar form of progressive multifocal leukoencephalopathy without immunodeficiency.

A case of the cerebellar form of progressive multifocal leukoencephalopathy (PML) without remarkable immune depression or immune deficiency … in the cerebellum, moderate and coalescent in the brainstem, and light and patchy in the cerebrum. JC virus antigen-positive cells were frequently observed in the demyelinated lesions in the cerebrum and sometimes observed in the brainstem, but were rarely found in the cerebellum. These findings suggest that PML lesions may be present with different degre …

Natalizumab for pediatric multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Pediatric-onset multiple sclerosis (POMS) is the onset of MS before the age of 18 and accounts for 3%-5% of all multiple sclerosis (MS) cases. Natalizumab (NTZ) is among the higher-efficacy disease-modifying treatments (HETs) in MS and is increasingly used for POMS. OBJECTIVES: In this systematic review and meta-analysis, we aimed to discuss the debate on the efficacy and safety of natalizumab use in POMS, providing quantitative results on relapse rate, disability progression, adverse events (AEs), and JC virus seropositivity. DESIGN: The primary endpoint for meta-analysis was th…

JC polyomavirus: a short review of its biology, its association with progressive multifocal leukoencephalopathy, and the diagnostic value of different methods to manifest its activity or presence.

INTRODUCTION: JC polyomavirus is the causative agent of progressive multifocal leukoencephalopathy (PML), a demyelinating disease resulting from the lytic infection of oligodendrocytes that may develop in immunosuppressed individuals: HIV1 infected or individuals under immunosuppressive therapies. Understanding the biology of JCPyV is necessary for a proper patient management, the development of diagnostic tests, and risk stratification. AREAS COVERED: The review covers different areas of expertise including the genomic characterization of JCPyV strains detected in different body compartments

Cerebellar progressive multifocal leucoencephalopathy identified by the shrimp sign.

Progressive multifocal leucoencephalopathy (PML) is a demyelinating disease caused by the John Cunningham (JC) virus, which may get reactiva … hrimp sign which raised the possibility of cerebellar PML, and the same was confirmed by a positive JC virus PCR in the cerebrospinal fluid. Our patient had no known immune-compromising state, but further workup revealed a low CD4 count suggestive of idiopathic CD4 lymphopenia. The case illustrates the importance of the shrimp sign on MRI, the possibility …

Neurologic complications in patients with inflammatory bowel disease: increasing relevance in the era of biologics.

Extraintestinal manifestations of inflammatory bowel disease (IBD) can involve almost every organ system. Neurologic complications are not i … ab has been associated with fatal progressive multifocal leukoencephalopathy due to reactivation of JC virus, and occurs with greater frequency in patients with previous JC virus infection. Stroke secondary to venous or arterial thromboembolism can be seen in patients with active Crohn's disease. It is important for gastroenterologists to be aware of the n …