Prior to this publication, The TrialNet Study Group evaluated rituximab, a beta cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1 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 analyzed the specific effect of rituximab on multiple islet autoantibodies. 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. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. 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.
Liping Yu, Kevan Herold, Heidi Krause-Steinrauf, Paula L. McGee, Brian Bundy, Alberto Pugliese, Jeff Krischer, George S. Eisenbarth, and for the Type 1 Diabetes TrialNet Anti-CD20 Study Group. (2011). Diabetes. 60:2560-2565.
Ramifications for Individuals with Type 1 Diabetes:
These studies highlight the unique properties of each of the islet autoantibodies, given that rituximab had a differential effect on their titers. Further studies are needed to confirm that the beneficial effect of rituximab is primarily due to its effect on reducing IAAs.
This research was funded, in part, by JDRF.