Rituximab selectively suppresses specific islet antibodies

Liping Yu, Kevan Herold, Heidi Krause-Steinrauf, Paula L. McGee, Brian Bundy, Alberto Pugliese, Jeff Krischer, George S. Eisenbarth

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48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2560-2565
Number of pages6
JournalDiabetes
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2011

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Yu, L., Herold, K., Krause-Steinrauf, H., McGee, P. L., Bundy, B., Pugliese, A., Krischer, J., & Eisenbarth, G. S. (2011). Rituximab selectively suppresses specific islet antibodies. Diabetes, 60(10), 2560-2565. https://doi.org/10.2337/db11-0674