title: Effect of rituximab on human in vivo antibody immune responses.
abstract: BACKGROUND
  B-lymphocyte depletion with rituximab has been shown to benefit patients with various autoimmune diseases. We have previously demonstrated that this benefit is also apparent in patients with newly diagnosed type 1 diabetes.
  
  
  OBJECTIVE
  The effect of rituximab on in vivo antibody responses, particularly during the period of B-lymphocyte depletion, is incompletely determined. This study was designed to assess this knowledge void.
  
  
  METHODS
  In patients with recent-onset type 1 diabetes treated with rituximab (n = 46) or placebo (n = 29), antibody responses to neoantigen phiX174 during B-lymphocyte depletion and with hepatitis A (as a second neoantigen) and tetanus/diphtheria (as recall antigens) after B-lymphocyte recovery were studied. Anti- tetanus, diphtheria, mumps, measles, and rubella titers were measured before and after treatment by means of ELISA. Antibody titers and percentage IgM versus percentage IgG to phiX174 were measured by means of phage neutralization. B-lymphocyte subsets were determined by means of flow cytometry.
  
  
  RESULTS
  No change occurred in preexisting antibody titers. Tetanus/diphtheria and hepatitis A immunization responses were protective in the rituximab-treated subjects, although significantly blunted compared with those seen in the controls subjects, when immunized at the time of B-lymphocyte recovery. Anti-phiX174 responses were severely reduced during the period of B-lymphocyte depletion, but with B-lymphocyte recovery, anti-phiX174 responses were within the normal range.
  
  
  CONCLUSIONS
  During the time of B-lymphocyte depletion, rituximab recipients had a decreased antibody response to neoantigens and significantly lower titers after recall immunization with diphtheria and tetanus toxoid. With recovery, immune responses return toward normal. Immunization during the time of B-lymphocyte depletion, although ineffective, does not preclude a subsequent response to the antigen.
authors: Department of Surgery, Indiana University, Indianapolis, IN, USA.
authors: Mark D
authors: MD
authors: Pescovitz
authors: Troy R
authors: TR
authors: Torgerson
authors: Hans D
authors: HD
authors: Ochs
authors: Elizabeth
authors: E
authors: Ocheltree
authors: Paula
authors: P
authors: McGee
authors: Heidi
authors: H
authors: Krause-Steinrauf
authors: John M
authors: JM
authors: Lachin
authors: Jennifer
authors: J
authors: Canniff
authors: Carla
authors: C
authors: Greenbaum
authors: Kevan C
authors: KC
authors: Herold
authors: Jay S
authors: JS
authors: Skyler
authors: Adriana
authors: A
authors: Weinberg
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002469:Cell Separation; D017322:Clinical Trials, Phase II as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab