Increased T Cell Proliferative Responses to Islet Antigens Identify Clinical Responders to Anti-CD20 Monoclonal Antibody (Rituximab) Therapy in Type 1 Diabetes
| Autor: | Kevan C. Herold, Zhugong Liu, Paula McGee, John M. Lachin, Kasia Bourcier, Heidi Krause-Steinrauf, Mark D. Pescovitz, H.-Michael Dosch, Lisa M. Spain, Adam Asare |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Time Factors Adolescent T cell Lymphocyte Immunology Autoantigens Article Antibodies Monoclonal Murine-Derived Antigen T-Lymphocyte Subsets Insulin-Secreting Cells Diabetes mellitus medicine Humans Immunologic Factors Immunology and Allergy Child Cell Proliferation Type 1 diabetes C-Peptide biology business.industry medicine.disease Diabetes Mellitus Type 1 medicine.anatomical_structure Monoclonal biology.protein Female Rituximab Antibody business medicine.drug |
| Zdroj: | The Journal of Immunology. 187:1998-2005 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|