Rituximab Selectively Suppresses Specific Islet Antibodies

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.

Reference:

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.

JDRF Involvement:

This research was funded, in part, by JDRF.