BACKGROUND AND PURPOSE: The anti-John-Cunningham virus (JCV)-antibody serostatus and index are used in the risk stratification of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab. However, little information on these parameters is available for Asian countries. The purpose of this study was to determine the rate of seropositivity, index, and longitudinal index evolution in Korean patients with MS. METHODS: The antibody seroprevalence was analyzed in 355 samples from 187 patients with clinically isolated syndrome or MS using a second-generation, two-step, enzyme-linked immunosorbent assay. A 4-year longitudinal evaluation was applied to 66 patients. RESULTS: The overall antibody seroprevalence was 80% (n=149). Among antibody-positive patients, the index had a median value of 3.27 (interquartile range, 1.52–4.18), with 77% (n=114) and 56% (n=83) of patients having indices >1.5 and >3.0, respectively. The serostatus of 59 (89%) of the 66 patients did not change during the longitudinal analysis, while 3 (6%) of the 53 patients who were initially seropositive reverted to seronegativity, and 2 (15%) of the 13 patients who were initially seronegative converted to seropositivity. All patients with a baseline index >0.9 maintained seropositivity, and 92% of patients with a baseline index >1.5 maintained this index over 4 years. No patients developed PML (median disease duration, 8 years). CONCLUSIONS: The seroprevalence and index of anti-JCV antibodies in Korean patients with MS may be higher than those in Western countries.
Antibodies ; Asia ; Asian Continental Ancestry Group ; Enzyme-Linked Immunosorbent Assay ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Multiple Sclerosis ; Natalizumab ; Seroepidemiologic Studies

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
Adolescent ; Adult ; Antibodies ; Brain ; Humans ; JC Virus* ; Leukoencephalopathy, Progressive Multifocal ; Multiple Sclerosis* ; Natalizumab ; Neuromyelitis Optica* ; Polyomavirus ; Prevalence*

Progressive multifocal leukoencephalopathy (PML) is a rare and lethal central nervous demyelinating disease caused by JC polyomavirus (JCV), particularly in patients with impaired immune system. The variation of JCV plays an important role in the pathogenesis of PML, including the recombination of non-coding regulatory region (NCCR), which is closely related to binding sites of transcription factors and affect the level of gene transcription. Nucleotide mutations in VP1 region determine the antigenicity and receptor specificity of JCV, play an important role in cell adsorption, immune-mediation and pathogenicity. In addition, immune cells are also involved in the pathogenesis of PML. T lymphocytes can recognize virus antigens, clear JCV, which are directly related to the prognosis of PML. B lymphocytes can serve as latent sites of JCV, and participate in viral transmission, replication, and coordination of the expression of transcription factors. This paper summarizes the roles of JCV variation and immune cells in pathogenesis of PML.
B-Lymphocytes ; immunology ; virology ; Capsid Proteins ; genetics ; immunology ; Humans ; JC Virus ; immunology ; Leukoencephalopathy, Progressive Multifocal ; pathology ; virology ; Mutation ; T-Lymphocytes ; immunology ; virology

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals.METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase.RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%).CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
Adolescent ; Adult ; Antibodies ; Brain ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Multiple Sclerosis ; Natalizumab ; Neuromyelitis Optica ; Polyomavirus ; Prevalence

Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton’s tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.
Antibodies, Monoclonal ; Immune System ; Immunocompromised Host ; JC Virus ; Leukemia, Lymphocytic, Chronic, B-Cell* ; Leukoencephalopathy, Progressive Multifocal* ; Protein-Tyrosine Kinases ; Rituximab

The JC virus is a widely infected human polyomavirus. Recent foreign researches showed that the JC virus infection is correlated with tumors of nervous system and digestive system, while, and study on the relationship between JC virus infection and gynecological tumor is seldom reported. In this study, we first establish the nucleic acid detection methods and procedures for JC virus and its highly homologous BK virus. The JC and BK viruses infection was evaluated by detect the viral DNA in samples including biopsy tissues, serum as well as urine of myoma of uterus (98 cases), cervical cancer (84 cases), endometrial cancer (40 cases) and ovarian tumor (72 cases) patients. The BK viral DNA positive rate was significantly higher in urine samples than that of blood and biopsy samples, and there is no significant difference of the BK viral DNA positive rate among all patient groups. The JC viral DNA positive rate is almost 0 in serum samples and biopsy. tissues, however, viral DNA positive rate is more than 50% in urine samples. In fibroids group, the JC viral DNA positive rate is up to 65. 3% which is significantly higher than that in other patients groups and healthy control. Further gynecological tumor associated viruses detection showed that only human papilloma virus infection is associated with cervical cancer, the herpes simplex virus, EB virus and cytomegalovirus infection is extremely low in our patient groups. No synergistic effect on gynecological tumor caused by viruses co-infection was observed. Our study showed that JC virus infection is highly related to the pathogenesis of uterine fibroids.
Adult ; Female ; Genital Neoplasms, Female ; virology ; Humans ; JC Virus ; classification ; genetics ; isolation & purification ; Middle Aged ; Polyomavirus Infections ; virology ; Tumor Virus Infections ; virology ; Young Adult

The characteristics of virus-like particle (VLP) of JC virus (JCV) as a vector for targeting gene delivery was determined. The exogenous DNA (PUC19) packaged in VLP-Z was resistant to DNase I. VLP-Z was able to deliver a reporter plasmid pEGFP-N1 into HeLa cells and the green fluorescent reporter protein was expressed in these cells. VLP-Z was also able to bind IgG by interaction with the Z fragment of VLP-Z and IgG. These results suggested that VLP-Z might be used as a vector to deliver therapeutic genes to target cells with incorporating IgG antibodies.
Gene Targeting ; methods ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Genetic Vectors ; genetics ; HeLa Cells ; Humans ; Immunoglobulin G ; metabolism ; JC Virus ; genetics ; metabolism ; Virion ; genetics ; metabolism

Posttransplantation lymphoproliferative disease (PTLD) is an important form of posttransplant malignancy and is typically associated with Epstein-Barr virus (EBV). Progressive multifocal leukoencephalopathy (PML) is a demyelination disease caused by infection of the John Cunningham (JC) virus. Both PTLD and PML occur in the setting of an immunosuppressive state. Differentiating PTLD from PML is important because PTLD can be treated by reducing immunosuppressant agents or anti-B-cell antibody therapy. We report a case of EBV-related PTLD in a patient with latent JC virus.
Demyelinating Diseases ; Herpesvirus 4, Human ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Viruses

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the human polyomavirus JC virus. PML mainly occurs in immunocompromised patients. A 36-year-old man with no evidence of immunosuppresion presented seizures. MRI scans of brain showed multifocal lesions in the cerebral white matters. JC virus DNA was positive in the cerebrospinal fluid examined by JC virus PCR. We report a rare case of PML presenting as viral encephalitis that occurred in a healthy adult person.
Adult ; Brain ; Central Nervous System ; Demyelinating Diseases ; DNA ; Encephalitis, Viral ; Humans ; Immunocompromised Host ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Magnetic Resonance Imaging ; Polymerase Chain Reaction ; Seizures ; Viruses

Adult ; Aged ; Antimalarials ; therapeutic use ; Female ; Humans ; Immune Reconstitution Inflammatory Syndrome ; drug therapy ; JC Virus ; immunology ; Leukoencephalopathy, Progressive Multifocal ; drug therapy ; Male ; Mefloquine ; therapeutic use ; Middle Aged ; Treatment Outcome