title: Rituximab inhibits the in vivo primary and secondary antibody response to a neoantigen, bacteriophage phiX174.
abstract: The response to primary immunization in patients treated with Rituximab (RIT) is not clear. We studied the in vivo antibody response of chronic renal failure (CRF) patients to the neoantigen bacteriophage phiX174 given alone or after ablation with RIT. Eighteen CRF subjects received two immunizations with phiX174 separated by 6 weeks. Nine subjects received a single dose of RIT. The intensity and immunoglobulin isotype of the antibody response (K(v)) were measured post-infusion. In addition, three subjects previously immunized and treated with RIT underwent a third and fourth immunization with phiX174 and a tetanus control 2 years later. RIT significantly decreased peak K(v) responses when compared to both historic non-CRF controls and to CRF subjects. CRF itself decreased peak K(v) responses compared to non-CRF controls. Percent-ratio of anti-phage IgM to IgG was significantly decreased in RIT treated subjects. One of three subjects treated with RIT was found to have developed a partial B cell tolerance to phiX174 administration 2 years later. RIT decreases antibody production and isotype switching to neoantigens and might be useful to prevent antibody response to therapeutic drugs and to newly transplanted organs.
authors.affiliation: Department of Surgery, Indiana University, Indianapolis, IN, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bearden
authors.forename: Avinash
authors.initials: A
authors.lastname: Agarwal
authors.forename: Benita K
authors.initials: BK
authors.lastname: Book
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Vieira
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sidner
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Marquerite
authors.initials: M
authors.lastname: Young
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pescovitz
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral / Q000737:chemistry; D000917:Antibody Formation; D000970:Antineoplastic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D010584:Bacteriophage phi X 174 / Q000276:immunology*; D001835:Body Weight; D005260:Female; D006085:Graft Survival; D006801:Humans; D007114:Immunization; D007136:Immunoglobulins / Q000737:chemistry; D016130:Immunophenotyping; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D000970:Antineoplastic Agents; D007136:Immunoglobulins; D000069283:Rituximab