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.

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.

• Authors: 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, Type 1 Diabetes TrialNet Study Group
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 128 Issue 6 Pg. 1295-1302.e5 (Dec 2011) ISSN: 1097-6825 [Electronic] United States
• PMID: 21908031 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunologic Factors
• Rituximab

Topics

• Adult
• Antibodies, Monoclonal, Murine-Derived (pharmacology)
• Antibody Formation (drug effects)
• B-Lymphocytes (drug effects, immunology)
• Cell Separation
• Clinical Trials, Phase II as Topic
• Diabetes Mellitus, Type 1 (drug therapy)
• Double-Blind Method
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Humans
• Immunologic Factors (pharmacology)
• Male
• Randomized Controlled Trials as Topic
• Rituximab