The Value of BCG and TNF in Autoimmunity
- 1st Edition - March 13, 2014
- Imprint: Academic Press
- Editor: Denise Faustman
- Language: English
- Paperback ISBN:9 7 8 - 0 - 1 2 - 7 9 9 9 6 4 - 7
- eBook ISBN:9 7 8 - 0 - 1 2 - 8 0 0 4 6 1 - 6
The Value of BCG and TNF in Autoimmunity provides an overview of current research and thinking related to tumor necrosis factor (TNF) induction and the use of the bacillus Calme… Read more
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Request a sales quoteThe Value of BCG and TNF in Autoimmunity provides an overview of current research and thinking related to tumor necrosis factor (TNF) induction and the use of the bacillus Calmette-Guérin (BCG) vaccine as potential treatment approaches to diverse forms of autoimmunity. BCG, commonly known as an anti-tuberculosis vaccine, is being explored in worldwide clinical trials as an approach to the treatment of certain forms of autoimmunity. The scope of research behind this therapeutic approach spans from the basic science of TNF signaling to research in diverse autoimmune disciplines, such as type 1 diabetes and multiple sclerosis.
Overall, the book focuses on the lessons that can be learned from the researchers' individual experiences and data, and provides a rationale for bringing the inexpensive, generic BCG vaccine to the forefront of clinical trials in different forms of autoimmunity.
- Editor awarded 2005: Oprah Achievement Award," Top Health Breakthrough by a Female Scientist"
- Brings into one resource the international scientific literature on a unique way to treat autoimmunity
- Provides a different perspective on treatment approaches for certain autoimmune conditions
- Discusses TNF induction, rather than anti-TNF, as a therapeutic pathway for autoimmunity treatment
Clinical researchers and scientists working in the fields of autoimmunity and/or immunology
Chapter 1. Mycobacteria, Immunoregulation, and Autoimmunity
- 1.1 Introduction
- 1.2 Increases in Inflammatory Disorders
- 1.3 Progressive Loss of Microbial Inputs
- 1.4 Old Friends and Immunoregulation
- 1.5 Humans and Mycobacteria
- 1.6 Mycobacteria, TNF, and T1D
- 1.7 Conclusions
- References
Chapter 2. Prevention of Type 1 Diabetes and Its Recurrence by Immunotherapy with Mycobacterial Adjuvants
- 2.1 Introduction
- 2.2 Mechanism of Action of AIT
- 2.3 Regeneration of Islet Cells by AIT
- 2.4 Microbiota and AIT
- 2.5 Conclusions
- Acknowledgements
- References
Chapter 3. Proteasome Defects and Cytokine Signaling in Sjögren’s Syndrome
- 3.1 Introduction
- 3.2 Involvement of the Proteasome System in Regulation of Foreign and Self-Directed Inflammation and Immunity
- 3.3 The Proteasome System in Sjögren’s Syndrome
- 3.4 Cytokine Signaling and Treatment Approaches in Sjögren’s Syndrome
- References
Chapter 4. The Protective Effect of the BCG Vaccine on the Development of Type 1 Diabetes in Humans
- 4.1 Introduction
- 4.2 Methods
- 4.3 Results
- 4.4 Discussion
- References
Chapter 5. Effects of the Bacillus Calmette-Guérin (BCG) Vaccine in the Demyelinating Disease of the Central Nervous System
- 5.1 Introduction
- 5.2 The BCG Vaccine in Patients with Relapsing-Remitting MS
- 5.3 BCG in People with Clinically Isolated Syndromes
- 5.4 The Future
- References
Chapter 6. TNF, BCG, and the Proteasome in Autoimmunity: An Overview of the Pathways & Results of a Phase I Study in Type 1 Diabetes
- 6.1 Introduction
- 6.2 Abnormal Class I Structures Generate Autoreactive T Cells
- 6.3 Defects in the Proteasome and Other HLA Class II-Linked Proteins for Loading of Peptides onto Class I Structures
- 6.4 The Links Between the Proteasome, TNF, and NF-κB: Clues to a New Treatment Approach
- 6.5 Advanced Type 1 Diabetes in NOD Mice is Reversed with TNF or TNF Induction by BCG
- 6.6 Humans with a Diversity of Autoimmune Diseases Have Autoreactive T Cells that Die from TNF or TNFR2 Agonism
- 6.7 BCG: The 90+-Year-Old Generic Drug Advances in Autoimmune Drug Trials
- 6.8 The TNF Signaling Pathway is Interrupted in Many Autoimmune Diseases
- 6.9 Summary and Conclusions
- References
Chapter 7. Why Test BCG in Sjögren’s Syndrome?
- 7.1 Introduction
- 7.2 Diagnosis
- 7.3 Symptoms and Signs
- 7.4 Pathogenesis
- 7.5 Therapeutic Options for Primary Sjögren’s Syndrome
- 7.6 Overview of Current Pharmacological Approaches
- 7.7 BCG Vaccination: A Method to Increase TNF-α Levels and a Potential New Therapy for Sjögren’s Syndrome
- 7.8 What is TNF-α?
- 7.9 What are the Advantages of High Levels of TNF-α?
- 7.10 What are the Disadvantages of Low Levels of TNF-α?
- 7.11 Anti-TNF-α Therapy: How Can it Work and How Can it Hurt?
- 7.12 BCG Vaccination: What are the Direct Arguments for Use in SS, and What are the Counterarguments?
- 7.13 Conclusions
- Acknowledgement
- References
Chapter 8. Celiac Disease as a Model Disorder for Testing Novel Autoimmune Therapeutics
- 8.1 Introduction
- 8.2 Pathogenesis of an Immunogenic Disease
- 8.3 BCG and the Role of TNF in Celiac Disease
- 8.4 Diagnosis: Current Approaches
- 8.5 High Prevalence of Celiac Disease
- 8.6 Mortality and Celiac Disease
- 8.7 The Burden of the Gluten-Free Diet
- 8.8 Gluten Challenge
- 8.9 The Rationale for Novel Therapeutic Approaches in Celiac Disease
- 8.10 Enzymatic Degradation: Endopeptidases
- 8.11 Larazotide Acetate: Tight Junction Regulator
- 8.12 Immune Modulation and Tolerance Induction: Necator americanus
- 8.13 Therapeutic Vaccine
- 8.14 Biological Therapies
- 8.15 IL-15 Antagonists
- 8.16 CCR9
- 8.17 Steroids: Modulating Inflammation and the Activity of the Immune System
- 8.18 Conclusions
- References
Chapter 9. Delivering Solutions and Clinical Benefits for Diseases with Small and Intermediate-Size Patient Populations
- 9.1 Introduction
- 9.2 Drug Discovery and Development: A Time-Consuming, Costly, and High-Risk Process
- 9.3 Academic Research and Pharmaceutical R&D Complement Each Other in Delivering Clinical Benefits to Patients
- 9.4 Delivery of Clinical Benefits Has Been Most Successful for Diseases with Large Patient Populations
- 9.5 Delivery of Clinical Benefits for Diseases with Small and Intermediate-Size Patient Populations Remains a Medical Need
- 9.6 Alternative Strategies are Required to Deliver Clinical Benefits for Diseases with Small and Intermediate-Size Patient Populations
- 9.7 Approved Drugs: A Strategy to Deliver Clinical Benefits for Diseases with Small and Intermediate-Size Patient Populations
- 9.8 Conclusion and Future Perspectives
- References
- Edition: 1
- Published: March 13, 2014
- Imprint: Academic Press
- No. of pages: 164
- Language: English
- Paperback ISBN: 9780127999647
- eBook ISBN: 9780128004616
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Denise Faustman
Denise L. Faustman, MD, PhD, is Director of the Immunobiology Laboratory at the Massachusetts General Hospital (MGH) and an Associate Professor of Medicine at Harvard Medical School. She has worked in the field of autoimmunity for nearly two decades. In 2001, the Faustman Lab reversed type 1 diabetes in mice with end-stage disease, a project that is now in human clinical trials. Dr. Faustman’s current research is focused on uncovering new treatments for type 1 diabetes, as well as searching for therapies for other autoimmune diseases, including Crohn's disease, lupus, scleroderma, rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis.
Dr. Faustman’s earlier research achievements include key discoveries regarding the role of MHC Class I antigen presentation in immunity and introducing the concept of modifying antigens on donor tissues to prevent their rejection. After completing her internship, residency, and fellowships in Internal Medicine and Endocrinology at the MGH, Dr. Faustman became an independent investigator at the MGH and Harvard Medical School in 1987. She is a member of the American Association for the Advancement of Science (AAAS) and serves as a frequent member of the Institute of Medicine in Washington, DC.
Dr. Faustman's honors in recent years include:
- 2003: National Institutes of Health and the National Library of Medicine, "Changing the Face of Medicine" award - one of 300 American physicians honored for achievement in medicine, past and present
- 2005: Oprah Achievement Award," Top Health Breakthrough by a Female Scientist"
- 2006: The American Medical Women's Association and Wyeth Pharmaceutical Company “Women in Science Award,” given to a female physician who has made exceptional contributions to medical science through basic science publications and leadership in the field
- 2011: The Goldman Philanthropic Partnerships/Partnership for Cures “2011 George and Judith Goldman Angel Award” for research to find an effective treatment for type 1 diabetes
Dr. Faustman is credited with the discovery of the role of CD8 T cells in type 1 diabetes, the discovery that HLA class I was an educational structure interrupted in self antigen presentation in autoimmunity, the discovery of first interruptions in the TNF and NFkB signaling pathway in autoimmunity in this case in the proteasome, the discovery that even end stage autoimmunity could be reversed in mice by the addition of TNF or TNF induction with BCG, the discovery of end organ pancreas regeneration in diseased animal models after BCG and more recently the discovery of functioning islet cells in the pancreas of the majority of human diabetics, decades after disease onset.
Affiliations and expertise
Director of the Immunobiology Laboratory, Massachusetts General Hospital (MGH) and Associate Professor of Medicine, Harvard Medical School, USARead The Value of BCG and TNF in Autoimmunity on ScienceDirect