title: Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes.
abstract: BACKGROUND
  Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses.
  
  
  OBJECTIVE
  To study the incidence of new infections and reactivations with BK, JC, Epstein-Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study.
  
  
  METHODS
  Subjects received 4 weekly doses of rituximab (N = 57) or placebo (N = 30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology.
  
  
  RESULTS
  EBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p < 0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p < 0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic.
  
  
  CONCLUSIONS
  Four doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses.
authors: Divison of Adult Infectious Diseases, University of Colorado School of Medicine, Aurora, USA.
authors: Jing Lu
authors: JL
authors: Kroll
authors: Craig
authors: C
authors: Beam
authors: Shaobing
authors: S
authors: Li
authors: Raphael
authors: R
authors: Viscidi
authors: Bonnie
authors: B
authors: Dighero
authors: Alice
authors: A
authors: Cho
authors: David
authors: D
authors: Boulware
authors: Mark
authors: M
authors: Pescovitz
authors: Adriana
authors: A
authors: Weinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001739:BK Virus / Q000235:genetics / Q000502:physiology; D002648:Child; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis / Q000097:blood / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000453:epidemiology / Q000628:therapy*; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology / Q000821:virology; D005260:Female; D006566:Herpesviridae Infections / Q000453:epidemiology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology; D006801:Humans; D015994:Incidence; D007577:JC Virus / Q000235:genetics / Q000502:physiology; D008297:Male; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000453:epidemiology* / Q000821:virology; D000069283:Rituximab; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000453:epidemiology* / Q000821:virology; D014766:Viremia / Q000453:epidemiology / Q000821:virology; D014775:Virus Activation; D017735:Virus Latency; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D004279:DNA, Viral; D000069283:Rituximab