Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes

Kevan C. Herold, Mark D. Pescovitz, Paula McGee, Heidi Krause-Steinrauf, Lisa M. Spain, Kasia Bourcier, Adam Asare, Zhugong Liu, John M. Lachin, H. Michael Dosch, C. J. Greenbaum, D. J. Becker, S. E. Gitelman, R. Goland, P. A. Gottlieb, J. B. Marks, P. F. McGee, A. M. Moran

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of β-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated β-cell loss. The way in which these responses affect the disease course remains unknown.

Original languageEnglish (US)
Pages (from-to)1998-2005
Number of pages8
JournalJournal of Immunology
Volume187
Issue number4
DOIs
StatePublished - Aug 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Herold, K. C., Pescovitz, M. D., McGee, P., Krause-Steinrauf, H., Spain, L. M., Bourcier, K., Asare, A., Liu, Z., Lachin, J. M., Dosch, H. M., Greenbaum, C. J., Becker, D. J., Gitelman, S. E., Goland, R., Gottlieb, P. A., Marks, J. B., McGee, P. F., & Moran, A. M. (2011). Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes. Journal of Immunology, 187(4), 1998-2005. https://doi.org/10.4049/jimmunol.1100539