Immunology of type 1 diabetes / edited by George S. Eisenbarth.

Format:

Book

Contributor:

Eisenbarth, George S.

Series:

Advances in experimental medicine and biology ; v.552.

Advances in experimental medicine and biology ; v.552

Language:

English

Subjects (All):

Diabetes--Immunological aspects.

Diabetes.

Diabetes Mellitus, Type 1--immunology.

Medical Subjects:

Diabetes Mellitus, Type 1--immunology.

Physical Description:

xvi, 335 pages ; 26 cm.

Edition:

Second edition.

Other Title:

Immunology of type one diabetes

Place of Publication:

New York : Kluwer Academic/Plenum Publishers ; Georgetown, Tex. : Landes Bioscience/Eurekah.com, [2004]

Summary:

In the field of immunology, type 1 diabetes has become one of the major areas of investigation with studies that span from characterization of key molecules to trials for the prevention of the disease. Type 1 Diabetes: Molecular, Cellular and Clinical Immunology communicates both the background and the most recent understanding of this disorder, which will almost certainly be central to elucidating the etiology of autoimmunity, and in particular of organ specific autoimmunity. The book covers immunogenetics, immunopathogenesis, epidemiology, disease prediction and clinical application of current knowledge. Both scientists seeking to understand and prevent type 1 diabetes/autoimmunity as well as physicians caring for families with type 1 diabetes will be interested in this book.

Contents:

1 Primer: Immunology/Autoimmunity / Stephanie C. Eisenbarth, George S. Eisenbarth 1

Normal Immune Response 1

Genetics of Autoimmunity 5

Triggering of Autoimmunity 6

Target Antigens 7

Effector Mechanisms 9

Therapy of Autoimmunity 9

2A Cell Therapy of Diabetes / Jan Nygaard Jensen, Jan Jensen 16

Islet Cell Transplantation - The Beginning of a New Era in Diabetes Treatment 16

The Cell Type in Demand: The Highly Specialized [beta]-Cell 17

The Beta-Cell: A Specialized Team-Player Packing a Punch but with a Poor Constitution 19

Overview of Possible [beta]-Cell Sources 21

[beta]-Cells from [beta]-Cells: Controlling Replication 22

Xenotransplantation 22

Embryonic Stem Cells - A Holy Grail or the Epitome of Man's Reduction of Life Through Science? 23

Differentiation of Embryonic Stem Cells into Insulin Producing Cells 23

The Active Selection Approach 23

The Culture Refinement Approach 25

Promises and Pitfalls on the Path to a Cure for Diabetes Using ES Cells 25

Therapeutic Cloning - Taking Advantage of Person-Specific Stem Cells 26

Adult Stem Cells a Resource for Tissue Homeostasis and Regeneration - And Perhaps Conversion 27

Plasticity of Adult Stem Cells 27

Liver 27

Modified GIP Cells: Intestinal Rescue of a Pancreatic Problem 28

Endocrine Tumor Cells 29

Regeneration of [beta]-Cells from Pancreatic Tissue 30

Reprogamming Cells - Where Do We Get a Grip? 33

What Technology Is Acceptable - And What Does the Patient with Diabetes Wish? 34

2B Proprotein Processing and Pancreatic Islet Function / John Hutton, Christina Wasmeier, Rodabe Amaria, Nicholas Bright, John Creemers 39

The Islet as a Neuroendocrine Organ 41

The Regulated Pathway of Polypeptide Secretion 42

The Enzymology of Pancreatic Hormone Proteolysis 44

Pathways of Prohormone Processing in the Endocrine Pancreas 46

Regulation of Prohormone Processing Activity within the Secretory Pathway 50

The Structure of PC1, PC2 and CPE and Their Post-Translational Processing 51

Antiproteases and Chaperones 53

Inherited Defects in Prohormone Processing in the Islet 53

Proprotein Processing Peturbations of Nongenetic Origin 56

Processing of Islet Autoantigens and Type 1A Diabetes 58

2C Stimulus-Secretion Coupling in the Pancreatic Beta-Cell / Kirstine Juhl, John Hutton 66

Physiology of the Islet of Langerhans 66

The Biosynthesis of Insulin 67

Physiological Regulation of Islet Hormone Secretion 68

Islet Pathophysiology in Type 1 Diabetes 69

The Stimulus-Secretion Coupling of the Pancreatic [beta]-Cell 71

3 Animal Models of Type 1 Diabetes: Genetics and Immunological Function / Julie Lang, Donald Bellgrau 91

The Nonobese Diabetic Mouse 91

Genetics of Diabetogenesis in the NOD Mouse 92

Immunology of the NOD Mouse 96

TCR Tg Mouse Models of Type 1 Diabetes 99

Transgenic Expression of NeoSelf-Antigens in Pancreas and Diabetes Incidence 101

Human Autoimmunity Genes Expressed as Transgenes in Mice 103

BioBreeding Diabetes-Prone (BB-DP) Rat Model of Spontaneous Type 1 Diabetes 103

Derivation of BB Rats 104

Genetics of BB Rats 104

Immune Dysfunction in the BB-DP Rat and Its Relationship to Lymphopenia 104

Activation and Death of T Cells Homozygous for lyp Mutation 106

The lyp Paradox 107

Disease Prevention in the BB-DP Rat 107

Long Evans Tokushima Lean (LETL) Rat Model 108

4 The Role of T Cells in Beta Cell Damage in Nod Mice and Humans / Katalin Kelemen 117

The NOD Mouse 117

Adoptive Transfer of Diabetes by T Cells 117

Checkpoints in the Development of Autoimmune Diabetes 118

T Cell Subsets in Type 1A Diabetes 118

Mechanism and Mediators of Beta Cell Death 119

The Autoantigens 120

Results from Investigations of Human Subjects 122

Histological Investigations 122

Demonstration of in Vitro T Cell Reactivity to Islet Cell Antigens 122

Problems Associated with the Detection of T Cell Reactivity in Diabetes - Conclusions from the First International T Cell Workshop 123

5 Type 1 Database Mellitus: An Inflammatory Disease of the Islet / Regine Bergholdt, Peter Heding, Karin Nielsen, Runa Nolsoe, Thomas Sparre, Joachim Storling, Jorn Nerup, Flemming Pociot, Thomas Mandrup-Poulsen 129

Genetic Aspects of the Inflammatory Model for the Pathogenesis of Type 1 Diabetes 131

Expression Profiling Studies of Genes and Proteins Regulated by Inflammatory Mediators 136

Signal Transduction of Cytokine-Mediated [beta]-Cell Death 140

The MAPK Pathways 141

Effector Mechanisms of Cytokine Mediated [beta]-Cell Destruction 144

6 The Immunobiology of Pancreatic Islet Transplantation / Marilyne Coulombe, Ronald G. Gill 154

Pancreatic Islet Allografting: The Allograft Paradox 155

Antigenicity Versus Immunogenicity of MHC Alloantigens 157

Pancreatic Islet Xenografting: The Xenograft Paradox 158

Role of T Cell Subsets in Islet Graft Rejection: A Central Role for CD4 T Cells 160

The Role of Donor APCs in Allograft Versus Xenograft Immunity 162

Islet Xenografting in Autoimmune Diabetes 162

Future Direction: Donor-Specific Tolerance Induction 162

7 Type 1 Diabetes Mellitus of Man: Genetic Susceptibility and Resistance / Alberto Pugliese, George S. Eisenbarth 170

Inherited Susceptibility Loci 171

The Major Susceptibility Locus IDDM1 171

The Insulin Gene-VNTR Locus IDDM2 177

Other Susceptibility Loci 187

Parental Effects on Inherited Genes Expression 187

Other Nonmendelian Regulatory Mechanisms 188

"Acquired" Genetic Polymorphisms 190

8 Autoimmune Polyendocrine Syndromes / George S. Eisenbarth 204

Autoimmune Polyendocrine Syndrome Type II (APS-II, Schmidt's Syndrome) 204

Therapy 209

Autoimmune Polyendocrine Syndrome Type I (APS-I) 210

XPID (X-Linked Polyendocrinopathy Immune Dysfunction) and Diarrhea 210

Anti-Insulin Receptor Antibodies 210

Thymic Tumors 210

POEMS Syndrome 211

Insulin Autoimmune Syndrome (Hirata Syndrome) 211

Other Disorders 211

9 Epidemiology of Type 1 Diabetes Mellitus / Marian Rewers, Jill Norris, Dana Dabelea 219

Type 1 Diabetes 219

Natural History of Type 1A Diabetes 219

Clinical Onset of Type 1 Diabetes 221

Incidence of Type 1 Diabetes 222

Remission ("Honeymoon Period") 229

Established Diabetes 229

Mortality 230

Coronary Artery Disease 233

10 Humoral Autoimmunity / Liping Yu, George S. Eisenbarth 247

Islet Cell Autoantibodies (ICAs) 248

Sequenced Autoantigens 249

Partially Characterized Autoantigens 257

Other Autoantigens 258

T Cell Reactivity 259

11 Prediction of Type 1 Diabetes: The Natural History of the Prediabetic Period / George S. Eisenbarth 268

Predictive Factors in Relatives 268

Prediction in the General Population 271

Prediction/Diagnosis in Adults 272

At What Stage in Life Is Beta Cell Autoimmunity Initiated? What Is the Initial Target Antigen, and in What Sequence Do Different Autoantibodies Appear? 272

Are Environmental Factors Important Either in the Initiation of Beta Cell Autoimmunity or in Modulating the Process Once it Has Begun? 274

Once Autoimmunity Is Initiated Are Beta Cells Destroyed in a Progressive Linear Fashion or Are There Spontaneous Remissions? 276

12 Clinical Trials for the Prevention of Type 1 Diabetes / H. Peter Chase, Anthony R. Hayward, George S. Eisenbarth 291

Animal Models for Type 1 Diabetes Prevention 291

Clinical Trials for the Prevention of Type 1 Diabetes 292

Trials in Newly Diagnosed Subjects 293

Other Immunosuppressive Agents (Rapamycin, Mycophenolate Mofetil, Anti-IL-2 Antibodies, Methotrexate) 293

Anti-CD3 Therapy 294

High Dose Intravenous Insulin 294

Immunostimulation 294

Identification of Subjects with PreType 1 Diabetes 294

Genetics 295

Immunological 296

Metabolic Testing 297

Trials Using Subjects with PreType 1 Diabetes 298

Nicotinamide 298

Additional Clinical Trials of Antigen Based Therapies 301

Theoretical Essay A Type 1 Diabetes: Molecular, Cellular and Clinical Immunology / George S.

Eisenbarth 306

Theoretical Essay B Can Getting Excited Over Nothing Provoke Autoimmunity? / Donald Bellgrau 311

Theoretical Essay C Pathogenesis of Type 1 Diabetes: A Viewpoint / Matthias G. von Herrath 317

Theoretical Essay D Was There Type 1 Diabetes in the Olduvai Gorge? / David V. Serreze, Derry C. Roopenian 322.

Notes:

Rev ed. of: Type I diabetes. Oxford University Press, 1996.

Includes bibliographical references and index.

ISBN:

0306478714

OCLC:

53178279

Publisher Number:

9780306478710