title: Rituximab treatment in hepatitis C infection: an in vitro model to study the impact of B cell depletion on virus infectivity.
abstract: Hepatitis C virus (HCV) infected patients with vasculitis are often treated with the B-cell-depleting anti-CD20 antibody rituximab. Treatment reduces the cryoglobulins that cause vasculitis, yet it also leads to a transient increase in liver enzymes and HCV genomic RNA in the periphery. The mechanism underlying the increased viral load is unclear and both direct and indirect roles have been proposed for B cells in HCV infection. We previously reported that HCV can associate with B cells and can trans-infect hepatocytes. We established an in vitro assay to study the effect(s) of rituximab on B cell-associated HCV infectivity. Rituximab-mediated lysis of B cells in vitro increases the level of infectious HCV released from B cells. Our results, using a model where virus does not replicate in B cells, recapitulate observations seen in patients and may explain in part the rapid increase in blood HCV RNA observed after rituximab treatment.
authors: Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom. z.stamataki@bham.ac.uk
authors: Zania
authors: Z
authors: Stamataki
authors: Samantha
authors: S
authors: Tilakaratne
authors: David H
authors: DH
authors: Adams
authors: Jane A
authors: JA
authors: McKeating
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000737:chemistry; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D006526:Hepatitis C / Q000188:drug therapy*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008954:Models, Biological; D015233:Models, Statistical; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007155:Immunologic Factors; D007376:Interleukin-2; D000069283:Rituximab