Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes
| العنوان: | Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes |
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| المؤلفون: | Limei Wang, Denise L. Faustman, Liqin Ban, Guotong Man, Joseph Avruch, Douglas E. Burger, Richard Pompei, David A. Schoenfeld, Hui Zheng, David M. Nathan, Yoshiaki Okubo |
| المصدر: | PLoS ONE, Vol 7, Iss 8, p e41756 (2012) PLoS ONE |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Bacterial Diseases, Male, Herpesvirus 4, Human, Anatomy and Physiology, T-Lymphocytes, lcsh:Medicine, Autoimmunity, medicine.disease_cause, Placebos, Endocrinology, 0302 clinical medicine, Pediatric Endocrinology, Immune Physiology, Insulin-Secreting Cells, Pathology, Cytotoxic T cell, lcsh:Science, Vaccines, 0303 health sciences, Multidisciplinary, C-Peptide, T Cells, Glutamate Decarboxylase, Vaccination, Middle Aged, 3. Good health, BCG Vaccine, Cytokines, Medicine, Infectious diseases, Female, Research Article, Adult, Clinical Research Design, Immune Cells, Viral diseases, Autoimmune Diseases, 03 medical and health sciences, Immune system, Double-Blind Method, Diagnostic Medicine, Immunity, Diabetes mellitus, Vaccine Development, medicine, Tuberculosis, Humans, Clinical Trials, Biology, 030304 developmental biology, Autoantibodies, Diabetic Endocrinology, Type 1 diabetes, business.industry, Tumor Necrosis Factor-alpha, lcsh:R, Case-control study, Diabetes Mellitus Type 1, medicine.disease, Diabetes Mellitus, Type 1, Case-Control Studies, Immunology, Epstein-Barr virus infectious mononucleosis, Clinical Immunology, lcsh:Q, business, BCG vaccine, 030217 neurology & neurosurgery, Biomarkers, General Pathology |
| الوصف: | Background No targeted immunotherapies reverse type 1 diabetes in humans. However, in a rodent model of type 1 diabetes, Bacillus Calmette-Guerin (BCG) reverses disease by restoring insulin secretion. Specifically, it stimulates innate immunity by inducing the host to produce tumor necrosis factor (TNF), which, in turn, kills disease-causing autoimmune cells and restores pancreatic beta-cell function through regeneration. Methodology/Principal Findings Translating these findings to humans, we administered BCG, a generic vaccine, in a proof-of-principle, double-blind, placebo-controlled trial of adults with long-term type 1 diabetes (mean: 15.3 years) at one clinical center in North America. Six subjects were randomly assigned to BCG or placebo and compared to self, healthy paired controls (n = 6) or reference subjects with (n = 57) or without (n = 16) type 1 diabetes, depending upon the outcome measure. We monitored weekly blood samples for 20 weeks for insulin-autoreactive T cells, regulatory T cells (Tregs), glutamic acid decarboxylase (GAD) and other autoantibodies, and C-peptide, a marker of insulin secretion. BCG-treated patients and one placebo-treated patient who, after enrollment, unexpectedly developed acute Epstein-Barr virus infection, a known TNF inducer, exclusively showed increases in dead insulin-autoreactive T cells and induction of Tregs. C-peptide levels (pmol/L) significantly rose transiently in two BCG-treated subjects (means: 3.49 pmol/L [95% CI 2.95–3.8], 2.57 [95% CI 1.65–3.49]) and the EBV-infected subject (3.16 [95% CI 2.54–3.69]) vs.1.65 [95% CI 1.55–3.2] in reference diabetic subjects. BCG-treated subjects each had more than 50% of their C-peptide values above the 95th percentile of the reference subjects. The EBV-infected subject had 18% of C-peptide values above this level. Conclusions/Significance We conclude that BCG treatment or EBV infection transiently modified the autoimmunity that underlies type 1 diabetes by stimulating the host innate immune response. This suggests that BCG or other stimulators of host innate immunity may have value in the treatment of long-term diabetes. Trial Registration ClinicalTrials.gov NCT00607230 |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98626890c48979b7fb9a68432b915cfaTest https://pubmed.ncbi.nlm.nih.gov/23304723Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....98626890c48979b7fb9a68432b915cfa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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