Dataset Information

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.

SUBMITTER: Pescovitz MD

PROVIDER: S-EPMC3659395 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Publications

Effect of rituximab on human in vivo antibody immune responses.

Pescovitz Mark D MD Torgerson Troy R TR Ochs Hans D HD Ocheltree Elizabeth E McGee Paula P Krause-Steinrauf Heidi H Lachin John M JM Canniff Jennifer J Greenbaum Carla C Herold Kevan C KC Skyler Jay S JS Weinberg Adriana A

The Journal of allergy and clinical immunology 20110909 6

<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>In patients with recent-onse ...[more]

PMID: 21908031

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Project description:BackgroundEx-vivo lung perfusion (EVLP) is an innovative platform for assessing donor lungs in the pre-transplant window. In this study, we demonstrate an extension of its utility by administering the anti-CD20 monoclonal antibody, Rituximab, during EVLP. We hypothesized that this would lead to targeted depletion of allograft B-cells which may provide significant clinical benefit, including the potential to reduce latent Epstein-Barr virus (EBV) and decrease the incidence of post-transplant lymphoproliferative malignancies.MethodsTwenty human donor lungs rejected for transplantation were placed on EVLP with (n = 10) or without (n = 10) 500 mg of Rituximab. Safety parameters such as lung physiology and inflammatory cytokines were evaluated. We measured the delivery efficacy through flow cytometry, immunohistochemistry and ELISA. An in-vitro culture assay, in the presence of complement, was further conducted to monitor whether B-cell depletion would occur in Rituximab-perfused samples.FindingsRituximab was successfully delivered to human lungs during EVLP as evidenced by flow cytometric binding assays where lung tissue and lymph node biopsies demonstrated occupied CD20 epitopes after perfusion with the antibody. Lymph nodes from Rituximab perfusions demonstrated a 10.9 fold-reduction in CD20+ staining compared to controls (p = 0.0003). In lung tissue, Rituximab resulted in an 8.75 fold-reduction in CD20+ staining relative to controls (p = 0.0002). This decrease in CD20+ binding illustrates the successful delivery and occupation of epitopes after perfusion with the Rituximab. No apparent safety concerns were seen as exhibited by markers associated with acute cell injury (e.g., proinflammatory cytokines), cell death (e.g., TUNEL staining), or pulmonary physiology. In a post-perfusion tissue culture model, the addition of complement (human serum) resulted in evidence of B-cell depletion consistent with what would be expected with posttransplant activation of bound Rituximab.InterpretationOur experiments illustrate the potential of EVLP as a platform to deliver monoclonal antibody therapies to treat donor lungs pretransplant with the goal of eliminating a latent virus responsible for considerable morbidity after lung transplantation.FundingSupported by the University Health Network Transplant Center.

Dataset Information

Effect of rituximab on human in vivo antibody immune responses.

Background

Objectives

Methods

Results

Conclusions

Publications

Effect of rituximab on human in vivo antibody immune responses.

Similar Datasets

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