Defining Optimal Immunotherapies for Type 1 Diabetes

• This book is a comprehensive and up-to-date account of where we stand in immunological strategies for preventing or treating type 1 diabetes (T1D).
• Brings together contributions from the leaders in the arena of clinical immunotherapy, not limited to the diabetes field exclusively, in order to delineate a road-map that would lead to future clinical trials.
• The book integrates information from human and animal studies.
• The book considers T1D within the broader context of autoimmune disease.
• The format contains several discussions, which address specific questions and provides guidelines for future strategies and solutions for discovering a cure.

1. Michael Rutter

Introduction: whither gene–environment interactions?

2. Rudolf Uher

Gene–environment interaction: overcoming methodological challenges

Discussion

3. Marco Battaglia, Cecilia Marino, Michel Maziade, Massimo Molteni and Francesca D’Amato

Gene–environment interaction and behavioural disorders: a developmental perspective based on endophenotypes

Discussion

4. Naomi R. Wray, William L. Coventry, Michael R. James, Grant W. Montgomery, Lindon J. Eaves and Nicholas G. Martin

Use of monozygotic twins to investigate the relationship between 5HTTLPR genotype, depression and stressful life events: an application of Item Response Theory

Discussion

Appendix

General discussion I

5. Harold Snieder, Xiaoling Wang, Vasiliki Lagou, Brenda W. J. H. Penninx, Harriëtte Riese and Catharina A. Hartman

Role of gene–stress interactions in gene-finding studies

Discussion

6. Kenneth A. Dodge

Practice and public policy in the era of gene–environment interactions

Discussion

7. Kristi B. Adamo and Frédérique Tesson

Gene–environment interaction and the metabolic syndrome

Discussion

General discussion II

8. Stephen P. Robertson and Richie Poulton

Longitudinal studies of gene–environment interaction in common diseases—good value for money?

Discussion

9. Kee-Seng Chia

Gene–environment interactions in breast cancer

Discussion

10. Malak Kotb, Nourtan Abdeltawab, Ramy Aziz, Sarah Rowe, Robert W. Williams and Lu Lu

Unbiased forward genetics and systems biology approaches to understanding how gene–environment interactions work to predict susceptibility and outcomes of infections

Discussion

11. Steven R. Kleeberger and Hye-Youn Cho

Gene–environment interactions in environmental lung diseases

Discussion

General discussion III

12. Fernando D. Martinez

Gene–environment interaction in complex diseases: asthma as an illustrative case

Discussion

13. Michael Rutter

Conclusions: taking stock and looking ahead

Glossary

Index of contributors

Subject index

The Novartis Foundation is an international scientific and educational charity which promotes the study and general knowledge of science and in particular encourages international co-operation in scientific research.

Type 1 diabetes (T1D) can be managed by administration of insulin, but the search continues for a more permanent cure. Hopes were high in the early 1990s, when the similarity between mouse and human MHC class II diabetes susceptibility genes had been discovered, and a cure seemed at hand via modulating interactions between CD4+ T cells and such MHC molecules. Unfortunately pathogenesis of T1D is much more complex, polygenic, dependent on disease penetrance on multiple environmental factors, and likely to involve the participation of CD4+, CD8+ and B lymphocytes. Additionally, islet β-cell destruction might involve mechanisms that differ among individuals.

Since T1D is an autoimmune disease, a likely strategy in this search for a cure seems to be modulation of the immune system. This book therefore brings together contributions from leaders in the arena of clinical immunotherapy, not limited to the diabetes field.

Topics discussed focus on the following questions:

• When and where does the co-ordination of the immune responses leading to islet destruction take place?
• What are the crucial histopathological features of human diabetes, and are these accurately reflected in mouse models?
• Can we define the functional features of pathogenic response, and can we assess whether these allow prediction of T1D development on an individual basis?
• Can we delineate a roadmap for successfully prioritizing and accelerating immunotherapeutics in T1D?

Defining optimal immunotherapies for type 1 diabetes offers a comprehensive and up-to-date account of immunological strategies for preventing or treating T1D, and will be of particular interest to diabetologists and endocrinologists, both clinicians and researchers, as well as to immunologists and molecular or cell biologists and drug discovery scientists. The book also considers T1D within the broader context of autoimmune disease, and is therefore of interest to clinicians and researchers working on any such disease.