JC Virus In Patients Research Articles

Prevalence of JC polyomavirus among rheumatoid arthritis and systemic lupus erythematosus patients and its correlation with vitamin D levels.

Vitamin D deficiency in viral infection associated with autoimmune diseases is well documented. This study assessed the prevalence of JC virus in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and its correlation with vitamin D level. Serum and urine samples were collected from 50 patients with RA and SLE. DNA was extracted and subjected to PCR test. Positive PCR products were sequenced, phylogenetic tree was constructed to determine the JC virus genotype. The patient's vitamin D level was evaluated. Of 50 patients, 19 (38%) were diagnosed as RA, and 31 (62%) were identified as SLE. JC virus DNA was detected in 17 (34%) patients' urine samples including 5 (26.3%) RA and 12 (38.7%) SLE cases. JC virus DNA was detected 2 (4%) in patients' serum samples (one RA. and one SLE). JC virus genotype 3A was dominant. Interestingly, the SLE patients with positive JC virus showed lowered vitamin D compared to patients with negative JC virus (P<0.005). Given the high rate of JC virus, DNA detection and susceptibility of patients for PML development, it is recommended that detection of JC virus DNA and vitamin D level should be implemented for patients with RA/SLE prior to treatment.

A new evaluation of the rearranged non-coding control region of JC virus in patients with colorectal cancer

HighlightsA significant proportion of 35/60 (58.33%) tumor tissue and 42/60 (70%) urine samples of the CRC patients were 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.screening JCV DNA in peripheral blood mononuclear cells (PBMCs) and stool of CRC patients may further support the potential for non-invasive screening tools.The study offers new insights into rearranged NCCR variants isolated from colorectal cancer (CRC) patients’ tissue.The screening and analysis of the rrNCCR region of JCV DNA in CRC patients’ stool may indicate the pathogenesis of the JCV virus in CRC development.The presence of JCV LTAg in tumor tissue is significantly higher than in normal tissue (p = < 0.002), suggesting JCV’s role in cancer development during the latency phase.

Prevalence and genotype distribution of JC polyomavirus in urine from patients with hematological malignancies in Vietnam.

JC virus (JCV) causes progressive multifocal leukoencephalopathy in immunocompromised patients. The prevalence and genotype patterns of JCV vary between different geographical regions. This study was done to investigate the prevalence and genotype distribution of JCV in patients with hematological malignancies in Vietnam. A total of 48 urine samples were collected from patients with hematological malignancies. DNA was extracted and detection of JCV was by nested-polymerase chain reaction. Sequence analysis was obtained and a phylogenetic tree was constructed for genotyping of JCV. Twenty-seven (56.25%) urine samples tested positive for JCV.JCV genotype 7 was only observed in this study. Subtype analysis showed that JCV subtype 7A was the most commonly prevalent, followed by 7B1 and 7C1. Other subtypes were not detected in this population. There were no significant differences associated with age, gender, and biochemical parameters between patients with JCV and without JCV excretion in urine. The present study showed a high prevalence of JCV in the urine of patients with hematologic malignancies. The most common genotype found in this population was JCV subtype 7A.

Prevalence of JC and BK viruses in Patients with Colorectal Cancer: A Systematic Review and Meta- Analysis.

Introduction:Polyomaviruses including BK virus (BKV) and JC virus (JCV) are widespread in human and have been associated with colorectal cancer (CRC) in some studies. The aim of present systematic review and meta-analysis article is to calculate the pooled prevalence of BKV and JCV in patients with CRC and assessing their association with this malignancy. Materials and Methods:Domestic databases and Sciences Direct, PubMed, ProQuest, Web of Sciences and Scopus were searched for relevant articles up to 2nd June 2019Two independent reviewers extracted the related data from eligible articles. The pooled prevalence and pooled odds ratio (POR) and their 95% confidence interval (95% CI) were calculated using “metaprop” and “metan” commands in Stata 14. Where I2 statistics were >50%, the random effect model was used. Results:From 1461 relevant studies, 24 articles were eligible and included in the qualitative while 19 articles included in quantitative analysis. The pooled prevalence based on diagnostic methods varies from 29% using immunohistochemistry to 52% using nested-PCR method. The likelihood of being infected with JCV was significantly higher in CRC patients compared to healthy (POR: 4.41, 95% CI: 2.13 – 9.13) controls, normal adjacent mucosa (POR: 2.79, 95% CI: 1.3-5.9) and colorectal adenoma (POR: 3.1, 95% CI: 1.5-6.5) but was not significant when non-CRC patients used as control group. Conclusion:The prevalence of JCV in colorectal patients was substantially variable by different methods and targets. The significant association between JCV and CRC that was observed in the present study is not indicative of causation and should be studied more in large-scale prospective designs.

Case report of a patient with progressive multifocal leukoencephalopathy under treatment with dimethyl fumarate

BackgroundProgressive multifocal leukoencephalopathy is a severe demyelinating disease caused by the polyoma JC virus in patients with reduced immunocompetence. A few cases of progressive multifocal leukoencephalopathy have been reported in patients treated with fumaric acid esters.Case presentationA 53-year-old Caucasian woman reported to our clinic with a first focal epileptic seizure and mild cognitive impairment. Since 1.5 years, she was treated with fumaderm for her psoriasis. During that time, her lymphocyte counts ranged between 450 and 700/μl. Cerebral magnet resonance imaging showed multifocal subcortical T2 hyperintense lesions with partial gadolinium enhancement. She did not have antibodies against human immunodeficiency virus 1 and 2 and cerebrospinal fluid-polymerase chain reaction for viral infections including a sensitive JC-virus polymerase chain reaction were negative. The diagnosis of progressive multifocal leukoencephalopathy was established by histological analysis and detection of JC-virus desoxyribonucleic acid in brain biopsy specimens. Dimethyl fumarate was stopped and Mirtazapin and Mefloquin were initiated. Neurological examination and imaging remained stable.ConclusionsProgressive multifocal leukoencephalopathy can occur in patients with lymphocyte counts between 450 and 700/μl, produce only faint symptoms and is not excluded by negative JC-virus-polymerase chain reaction in cerebrospinal fluid. The incidence of progressive multifocal leukoencephalopathy may thus be underestimated and a more careful surveillance of patients would be necessary.

Relevance of CD34+ cells as a reservoir for JC virus in patients with multiple sclerosis.

Relevance of CD34+ cells as a reservoir for JC virus in patients with multiple sclerosis.

Sa1974 Immune Response to the T Antigen of JC Virus in Patients With Colorectal Neoplasia Compared to Those Without

Sa1974 Immune Response to the T Antigen of JC Virus in Patients With Colorectal Neoplasia Compared to Those Without

Progressive Multifocal Leukoencephalopathy in a Patient Treated With Etanercept

Recently, increased attention has been paid to the association of progressive multifocal leukoencephalopathy (PML) with the use of immunomodulatory medications for autoimmune diseases. A 23-year-old Native American woman with a history of systemic lupus erythematosus and erosive polyarthritis treated with prednisone and etanercept presented with focal weakness, hemiataxia, diplopia, and dysarthria. Brain magnetic resonance imaging demonstrated progressive, T2 signal hyperintensities within the brainstem and cerebellar white matter without mass effect or gadolinium enhancement. Cerebrospinal fluid showed elevated protein and JC virus polymerase chain reaction positive with 28,600 copies/ml diagnostic of PML. The development of PML in this patient treated with etanercept and prednisone highlights the increased risk for opportunistic infection with JC virus in patients with autoimmune diseases on immunosuppressive therapies.

Frequent Infection of Cortical Neurons by JC Virus in Patients With Progressive Multifocal Leukoencephalopathy

The human polyomavirus JC (JCV) infects glial cells and causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, in immunosuppressed individuals. The extent of JCV infection of neurons is unclear. We determined the prevalence and pattern of JCV infection in gray matter (GM) by immunostaining in archival brain samples of 49 PML patients and 109 control subjects. Among PML patients, 96% had demyelinating lesions in white matter and at the gray-white junction (GWJ); 57% had them in the GM. Most JCV-infected cells in GWJ and GM were glia, but JCV also infected neurons in PML lesions at the GWJ of 54% and GM of 50% patients and in GM outside areas of demyelination in 11% of patients. The JCV regulatory T antigen (Ag) was expressed more frequently in cortical neurons than the VP1 capsid protein. None of the control subjects without PML had any cells expressing JCV proteins. Thus, the cerebral cortex often harbors demyelinating lesions of PML, and JCV infection of cortical neurons is frequent in PML patients. The predominance of T Ag over VP1 expression suggests a restrictive infection in neurons. These results indicate that JCV infection of cerebral cortical neurons is a previously under appreciated component of PML pathogenesis.

Asymptomatic Reactivation of JC Virus in Patients Treated with Natalizumab

Asymptomatic Reactivation of JC Virus in Patients Treated with Natalizumab

Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study

Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study

Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study

Natalizumab is used to prevent relapses and progression of disability in patients with multiple sclerosis but has been associated with progressive multifocal leukoencephalopathy (PML). We aimed to better understand the associations between JC virus, which causes PML, and natalizumab treatment. We prospectively assessed patients with multiple sclerosis who started treatment with natalizumab. Blood and urine samples were tested for the presence of JC virus DNA with quantitative real-time PCR before treatment and at regular intervals after treatment onset for up to 18 months. At the same timepoints, by use of proliferation and enzyme-linked immunospot assays, the cellular immune responses against JC virus, Epstein-Barr virus, cytomegalovirus, myelin oligodendrocyte glycoprotein, and myelin oligodendrocyte basic protein (MOBP) were assessed. Humoral immune response specific to JC virus was assessed with an enzyme immunoassay. The same experiments were done on blood samples from patients with multiple sclerosis before and 10 months after the start of interferon beta treatment. We assessed 24 patients with multiple sclerosis who received natalizumab and 16 who received interferon beta. In patients treated with natalizumab, JC virus DNA was not detected in the blood at any timepoint. However, JC virus DNA was present in the urine of six patients and in most of these patients the concentrations of JC virus DNA were stable over time. Compared with pretreatment values, the cellular immune response was increased to cytomegalovirus at 6 months, to JC virus at 1, 9, and 12 months, and to Epstein-Barr virus and MOBP at 12 months. Humoral responses remained stable. There were no increases in cellular immune responses specific to the viruses or myelin proteins in the 16 patients treated with interferon beta. Natalizumab increases cellular immune responses specific to viruses and myelin proteins in the peripheral blood after 1 year, without evidence of viral reactivation. Swiss National Foundation, Swiss Society for Multiple Sclerosis, and Biogen Dompé.

Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study

Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study

Asymptomatic Reactivation of JC Virus in Patients Treated with Natalizumab

Asymptomatic Reactivation of JC Virus in Patients Treated with Natalizumab

Asymptomatic Reactivation of JC Virus in Patients Treated with Natalizumab

Progressive multifocal leukoencephalopathy (PML) occurs in a fraction of patients with multiple sclerosis who were treated with natalizumab. Most adults who are infected with the JC virus, the etiologic agent in PML, do not have symptoms. We sought to determine whether exposure to natalizumab causes subclinical reactivation and neurotropic transformation of JC virus. We followed 19 consecutive patients with multiple sclerosis who were treated with natalizumab over an 18-month period, performing quantitative polymerase-chain-reaction assays in blood and urine for JC virus reactivation; BK virus, a JC virus-related polyomavirus, was used as a control. We determined JC virus-specific T-cell responses by means of an enzyme-linked immunospot assay and antibody responses by means of an enzyme-linked immunosorbent assay and analyzed JC virus regulatory-region sequences. After 12 months of natalizumab therapy, the prevalence of JC virus in the urine of the 19 patients increased from a baseline value of 19% to 63% (P=0.02). After 18 months of treatment, JC virus was detectable in 3 of 15 available plasma samples (20%) and in 9 of 15 available samples of peripheral-blood mononuclear cells (60%) (P=0.02). JC virus regulatory-region sequences in blood samples and in most of the urine samples were similar to those usually found in PML. Conversely, BK virus remained stable in urine and was undetectable in blood. The JC virus-specific cellular immune response dropped significantly between 6 and 12 months of treatment, and variations in the cellular immune response over time tended to be greater in patients in whom JC viremia developed. None of the patients had clinical or radiologic signs of PML. Subclinical reactivation of JC virus occurs frequently in natalizumab-treated patients with multiple sclerosis. Viral shedding is associated with a transient drop in the JC virus-specific cellular immune response.

The absence of JC virus antigens in Indian children with medulloblastomas

The human polyoma virus, also known as the JC virus (JCV), replicates predominantly in the oligodendrocytes, the myelin producing cells in the central nervous system and results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) especially in immunosuppressed patients with AIDS. Several investigators have also documented the presence of the viral genome and early and late antigens in a variety of brain tumors particularly in medulloblastomas, gliomas and ependymomas. Reports also indicate the presence of JCV in patients with colon cancer. The T antigen of JCV has been postulated to have oncogenic potential as substantiated by animal experiments. Although JCV infects 80% of the population, there are scant epidemiological studies regarding JCV from India. There are also reports of the low prevalence of PML in patients with AIDS from India and Africa. This study was undertaken to investigate if Indian children with medulloblastomas also show evidence of JCV. Twenty-two consecutive cases of medulloblastomas were investigated for the presence of T antigen and agnoprotein of JCV in biopsy specimens by immunohistochemistry. Antibodies to the agnoprotein antigen raised in rabbits and a monoclonal antibody against SV40 T antigen raised in mice that cross-reacts with JCV T antigen were used. Out of 22 patients, 4 had desmoplastic tumors while the rest had classical tumors. All children were below the age of 10. Results indicate that while PML tissues showed consistent immunostaining both with antibody to T antigen and agnoprotein antibody, none of the tumors showed any positive staining for JC viral antigens. JCV antigens could not be detected by immunohistochemistry in the tumor tissues of Indian children with medulloblastomas.

JC viral loads in patients with Crohn’s disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy?

Background and aims:Anti-α4 integrin therapy with natalizumab is efficacious in refractory Crohn’s disease and in multiple sclerosis, but carries an estimated 1/1000 risk of progressive multifocal leukoencephalopathy (PML) caused by...

Progressive multifocal leukoencephalopathy from JC virus in a patient with advanced mycosis fungoides

Progressive multifocal leukoencephalopathy is a central nervous system disease due to reactivation of the human polyoma JC virus in immunocompromised patients. Advanced mycosis fungoides patients are intrinsically immunosuppressed and susceptible to infections, but only rarely have been reported to develop progressive multifocal leukoencephalopathy. We report a case of progressive multifocal leukoencephalopathy developing in an advanced mycosis fungoides patient without prior history of immunosuppressive therapy.

Stability of JC virus coding sequences in a case of progressive multifocal leukoencephalopathy in which the viral control region was rearranged markedly.

It is generally accepted that JC virus variants in the brains of patients with progressive multifocal leukoencephalopathy are generated from archetypal strains through sequence rearrangement (deletion and duplication, or deletion alone) in the control region. This change is thought to occur during persistence of JC virus in patients. The present study was performed to ascertain whether amino acid substitution in the viral proteins is involved in the generation and propagation of JCV variants with rearranged control regions. Many complete JC DNA clones were established from brain tissues (cerebellum, occipital lobe, and brainstem) autopsied in a case of progressive multifocal leukoencephalopathy in which multiple distinct control sequences were detected. Control and coding sequences were determined and compared among the JC DNA clones. Twenty-eight control-region and 20 coding sequences of JC virus were compared. Five rearranged control sequences were detected, but they could be classified into 3 groups that shared common structural features. Viral coding sequences were identical among clones with different control regions and among clones derived from different brain regions. In the present case, nucleotide substitution in the viral coding regions (and resultant amino acid change in the viral proteins) was involved neither in the genesis of rearranged JC virus variants nor in the proliferation of demyelinated lesions in the brain.

Progressive Multifocal Leukoencephalopathy with Detection of JC Virus in a Patient with Chronic Lymphocytic Leukemia Parallel to Onset of Fludarabine Therapy

Along with the establishment of more intense chemotherapeutic regimens including fludarabine for the treatment of indolent lymphoproliferative diseases like chronic lymphocytic leukemia (CLL), an increasing amount of cases with progressive multifocal leukoencephalopathy (PML) due to JC virus have been observed. We report a patient with CLL who developed PML parallel to the onset of fludarabine therapy. Spinal fluid was tested positive for JC virus. Despite virostatic treatment with cidofovir, neurologic symptoms were progressive and the disease ultimately fatal. The present case suggests that immunosuppression caused by chronic lymphoproliferative malignancies alone may be a factor in the development of PML. Chemotherapy with fludarabine may act as an additional trigger. The question remains whether serologic screening for JC virus in patients with chronic lymphoproliferative disease undergoing intense chemotherapy might be valuable once sufficient antiviral treatment has been established.