Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec;128(6):1295-1302.e5.
doi: 10.1016/j.jaci.2011.08.008. Epub 2011 Sep 9.

Effect of rituximab on human in vivo antibody immune responses

Collaborators, Affiliations

Effect of rituximab on human in vivo antibody immune responses

Mark D Pescovitz et al. J Allergy Clin Immunol. 2011 Dec.

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.

PubMed Disclaimer

Conflict of interest statement

Disclosure of potential conflict of interest: T R. Torgerson has consultant arrangements with Baxter Biosciences. J. M. Lachin has consultant arrangements with Genentech, Bayhill Therapeutics, GlaxoSmithKline, and TolerRx. C. Greenbaum receives research support from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, the Juvenile Diabetes Research Foundation International, and the National Institutes of Health/National Institute of Allergy and Infectious Diseases. J. S. Skyler is on the Board of Directors for Amylin Pharmaceuticals and DexCom Inc, has consultant arrangements with SanofiAventis and BD Technologies, and has received research support from Bayhill Therapeutics, Halozyme Inc, and Osiris Therapeutics. The rest of the authors have declared that they have no conflict of interest.

Figures

Fig 1
Fig 1
Mean titers (and 95% confidence limits) for measles (A), mumps (B), rubella (C), tetanus (D), diphtheria (E), and hepatitis A (F) from a repeated-measures model with adjustments for baseline titer (except for hepatitis A because its baseline titer was not measured), age, and sex. Two-sided unadjusted P values are reported. Log transformation of antigen titer was used for all but mumps. Log values were transformed to normal scale for the figure.
Fig 2
Fig 2
Antibody response to phiX174 immunization over time in rituximab-treated and placebo-treated subjects and healthy control subjects (gray hatched area). Immunization times are indicated by arrows. Time 0 is before rituximab treatment. Healthy control subjects were only immunized 3 times. Geometric means were calculated by using natural logarithms and transformed back by means of exponentiation. P values are from a repeated-measures model.

Similar articles

Cited by

References

    1. Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998;92:1927–32. - PubMed
    1. McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825–33. - PubMed
    1. Tobinai K, Kobayashi Y, Narabayashi M, Ogura M, Kagami Y, Morishima Y, et al. Feasibility and pharmacokinetic study of a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) in relapsed B-cell lymphoma The IDEC-C2B8 Study Group. Ann Oncol. 1998;9:527–34. - PubMed
    1. Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994;84:2457–66. - PubMed
    1. Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009;361:2143–52. - PMC - PubMed

Publication types