Effect of rituximab on human in vivo antibody immune responses

Mark D. Pescovitz, Troy R. Torgerson, Hans D. Ochs, Elizabeth Ocheltree, Paula McGee, Heidi Krause-Steinrauf, John M. Lachin, Jennifer Canniff, Carla Greenbaum, Kevan C. Herold, Jay S. Skyler, Adriana Weinberg

Research output: Contribution to journalArticle

61 Scopus citations

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. Objectives: 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.

Original languageEnglish (US)
Pages (from-to)1295-1302.e5
JournalJournal of Allergy and Clinical Immunology
Volume128
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • antibodies
  • B lymphocytes
  • CD20
  • diabetes
  • human
  • immunization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Pescovitz, M. D., Torgerson, T. R., Ochs, H. D., Ocheltree, E., McGee, P., Krause-Steinrauf, H., Lachin, J. M., Canniff, J., Greenbaum, C., Herold, K. C., Skyler, J. S., & Weinberg, A. (2011). Effect of rituximab on human in vivo antibody immune responses. Journal of Allergy and Clinical Immunology, 128(6), 1295-1302.e5. https://doi.org/10.1016/j.jaci.2011.08.008