title: Assessment of the risk of polyomavirus JC reactivation in patients with immune-mediated diseases during long-term treatment with infliximab.
abstract: Polyomavirus JC (JCV) reactivation causing progressive multifocal leukoencephalopathy is a main concern during biological therapies. Here, JCV reactivation in patients suffering from immune-mediated diseases after a long-term treatment with anti-tumor necrosis factor alpha (TNF-α) inhibitor infliximab was investigated. Peripheral mononuclear blood cells (PBMC), plasma and urine samples were obtained from 61 immune-mediated diseases patients treated or not with infliximab in combination with steroid and other immunomodulators and from 20 healthy donors. JCV DNA was transiently detected in 12 PBMC of 40 patients at different doses of infliximab with a higher prevalence than that of the 21 patients untreated. Conversely, a stable JCV positivity in urine of treated and untreated patients was detected. Sequencing the noncoding control region (NCCR), all samples exhibited the archetype structure with few mutations in transcriptional factor binding regions. The consequence of anti-TNF-α treatment on viral persistence was examined monitoring Torquetenovirus viremia and investigating the TNF-α-induced microRNA regulators of transcriptional factors, with a binding site on NCCR. Although infliximab treatment in this study did not affect directly JCV reactivation, further investigation on host factor(s) regulated by it will be of warranty in the understanding the mechanism(s) that may affect viral persistence.
authors.affiliation: Virology Unit, Department of Public Health, University of Florence, Florence, Italy. simone.giannecchini@unifi.it
authors.forename: Simone
authors.initials: S
authors.lastname: Giannecchini
authors.forename: Valeria
authors.initials: V
authors.lastname: Clausi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vultaggio
authors.forename: Lisa
authors.initials: L
authors.lastname: Macera
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Maggi
authors.forename: Francesco
authors.initials: F
authors.lastname: Martelli
authors.forename: Alberta
authors.initials: A
authors.lastname: Azzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.forename: Andrea
authors.initials: A
authors.lastname: Matucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D000069285:Infliximab; D007577:JC Virus / Q000235:genetics* / Q000472:pathogenicity; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood / Q000276:immunology / Q000652:urine / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D014775:Virus Activation / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab