Loss of intra-islet CD20 expression may complicate efficacy of B-cell-directed type 1 diabetes therapies
Diabetes, ISSN: 0012-1797, Vol: 60, Issue: 11, Page: 2914-2921
2011
- 65Citations
- 30Captures
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Metrics Details
- Citations65
- Citation Indexes63
- 63
- CrossRef57
- Patent Family Citations2
- 2
- Captures30
- Readers30
- 30
Article Description
OBJECTIVE - Consistent with studies in NOD mice, early clinical trials addressing whether depletion of B cells by the Rituximab CD20-specific antibody provides an effective means for type 1 diabetes reversal have produced promising results. However, to improve therapeutic efficacy, additional B-cell-depleting agents, as well as attempts seeking diabetes prevention, are being considered. RESEARCH DESIGN AND METHODS - Autoantibodies, including those against insulin (IAAs), are used to identify at-risk subjects for inclusion in diabetes prevention trials. Therefore, we tested the ability of anti-CD20 to prevent diabetes in NOD mice when administered either before or after IAA onset. RESULTS - The murine CD20-specific 18B12 antibody that like Rituximab, depletes the follicular (FO) but not marginal zone subset of B cells, efficiently inhibited diabetes development in NOD mice in a likely regulatory T-cell-dependent manner only when treatment was initiated before IAA detection. One implication of these results is that the FO subset of B cells preferentially contributes to early diabetes initiation events. However, most important, the inefficient ability of anti-CD20 treatment to exert late-stage diabetes prevention was found to be attributable to downregulation of CD20 expression upon B cell entry into pancreatic islets. CONCLUSIONS - These findings provide important guidance for designing strategies targeting B cells as a potential means of diabetes intervention. © 2011 by the American Diabetes Association.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80755168884&origin=inward; http://dx.doi.org/10.2337/db11-0705; http://www.ncbi.nlm.nih.gov/pubmed/21926271; https://diabetesjournals.org/diabetes/article/60/11/2914/33481/Loss-of-Intra-Islet-CD20-Expression-May-Complicate; https://dx.doi.org/10.2337/db11-0705; https://diabetes.diabetesjournals.org/content/60/11/2914; https://diabetes.diabetesjournals.org/content/60/11/2914.abstract; https://diabetes.diabetesjournals.org/content/diabetes/60/11/2914.full.pdf; http://diabetes.diabetesjournals.org/cgi/doi/10.2337/db11-0705; http://diabetes.diabetesjournals.org/content/60/11/2914; http://diabetes.diabetesjournals.org/content/60/11/2914.abstract; http://diabetes.diabetesjournals.org/content/60/11/2914.full.pdf; http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db11-0705
American Diabetes Association
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