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Rituximab Selectively Suppresses Specific Islet Antibodies

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  • Additional Information
    • Publication Information:
      Alexandria, VA: American Diabetes Association, 2011.
    • Publication Date:
      2011
    • Original Material:
      INIST-CNRS
    • Abstract:
      OBJECTIVE—The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. RESEARCH DESIGN AND METHODS-A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. RESULTS-Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P < 0.0001). In the subgroup (n = 6) treated within 50 days of diabetes, IAAs were markedly suppressed by rituximab in all patients for 1 year and for four patients as long as 3 years despite continuing insulin therapy. Independent of rituximab treatment, the mean level of IAAs at study entry was markedly lower (P = 0.035) for patients who maintained C-peptide levels during the first year of follow-up in both rituximab-treated and placebo groups. CONCLUSIONS-A single course of rituximab differentially suppresses IAAs, clearly blocking IAAs for >1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.
    • File Description:
      text
    • Author Affiliations:
      Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, United States
      Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States
      Biostatistics Center, George Washington University, Rockville, Maryland, United States
      Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, New York, United States
      Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida, United States
      Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida, United States
    • ISSN:
      0012-1797
    • Rights:
      Copyright 2015 INIST-CNRS
      CC BY 4.0
      Sauf mention contraire ci-dessus, le contenu de cette notice bibliographique peut être utilisé dans le cadre d’une licence CC BY 4.0 Inist-CNRS / Unless otherwise stated above, the content of this bibliographic record may be used under a CC BY 4.0 licence by Inist-CNRS / A menos que se haya señalado antes, el contenido de este registro bibliográfico puede ser utilizado al amparo de una licencia CC BY 4.0 Inist-CNRS
    • Notes:
      Endocrinopathies
    • Accession Number:
      edscal.24592502