Treating Type 1 Diabetes By Eliminating B Cells

An antibody used to treat certain cancers and rheumatoid arthritis appears to greatly delay type 1 diabetes in mice, Yale School of Medicine researchers report.

"Even better, the beneficial effects of the antibody continue to be observed long after the antibody is no longer administered," the researchers said.

Depletion of the B cell subset of lymphocytes using an antibody specific for the protein CD20 has been shown to be effective for the treatment of RA. The effectiveness of such an approach for the treatment of type I diabetes is not known, largely because the reagents to address this question in preclinical models have been lacking.

This problem has now been overcome by Li Wen and colleagues from Yale School of Medicine, New Haven, who have developed the necessary tools and shown that depletion of B cells can both prevent diabetes and reverse established disease in mice. In the accompanying commentary, Hélène Bour-Jordan and Jeffrey Bluestone from the University of California, San Francisco, highlight the importance of these advances for developing and optimizing the potential of CD20-specific antibodies for the treatment of type 1 diabetes.

In the study, autoimmune diabetes--susceptible mice were engineered such that their B cells expressed human CD20. Depletion of B cells in these mice before they showed signs of diabetes, using a single dose of a CD20-specific antibody, delayed and/or reduced the onset of disease.

Similarly, in mice already showing signs of diabetes, a single dose of the CD20-specific antibody reversed disease in a substantial proportion of the mice. Furthermore, the mechanism behind the protection afforded by CD20-specific antibody treatment was shown to be associated with increased numbers of regulatory T cells and B cells.

"These studies suggest that B cells can have dual roles in diabetes and possibly other autoimmune diseases. The B cells might promote disease initially, but after being reconstituted following initial depletion with rituximab, they actually block further disease," Mark Shlomchik, M.D. of Yale University added. "This means that multiple rounds of medication to deplete the B cells might not be necessary or even advisable."

The article "Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice" is published in the Journal of Clinical Investigation on  December 3, 2007.