Preface

*Every coin has two sides.* The immune system, which protects us from diseases otherwise, can itself directly and evidently cause diseases. Due to failure in the process of tolerance induction and regulation, immune responses, when mistakenly directed against body's own components ('self' antigens), can result in long lasting and recurrent pathological damages to the targeted organs and tissues. These are collectively known as autoimmune disorders, ranging from various organ-specific ones, to those systemic in nature.

The term autoimmunity signifies the presence of self-reactive immune responses with antigen specificity and immunological memory, two key features of the adaptive immunity. Autoimmune responses however, are detected not only in patients with autoimmune diseases, but frequently in healthy individuals as well. The pathological consequence of these reactions depends, often due to lack of certain protective mechanisms, on the type of the responses induced. Some of these autoimmune reactions can even be beneficial; for example, in removing or dumping off various unwanted or aged tissue components. There is also convincing evidence indicating that such responses are involved into fight against tumors, i.e. the 'altered self'. The basis of autoimmunity is still far from being fully understood, although both genetic and environmental factors are believed to often contribute to the pathogenesis together. A good understanding of the autoimmune mechanisms is therefore important for effective diagnosis, as well as better treatment of many autoimmune diseases, and even further beyond.

In this book, thanks to many experts in the field who have made their valuable contributions as authors, updated information is gathered on various autoimmune disorders. These include some of the most classical and unique disease phenotypes, such as Hashimoto's thyroiditis, Type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, primary Sjogren syndrome, Sweet syndrome, multiple sclerosis and various other neurological and hematological disorders. Importantly, the book focuses on current advances and new concepts based on cutting-edge findings from both clinical and basic scientific studies. A total of 29 chapters are divided into 5 main sections according to the emphasis of their contents: (I) Disease phenotypes (Chapters 1-7), (II) Diagnostics & prognostics (Chapters 8-11), (III) Therapeutic interventions

#### XII Preface

(Chapters 12-20), (IV) Pathogenesis & underlying mechanisms (Chapters 21-25), and (V) Other conceptual advances & new insights (Chapters 26-29).

The primary aim of this book is to provide most up-to-date information in the 5 defined aspects as stated above, and in the form of Open Access in particular, to be freely available to both clinicians and basic scientists regarding current advances in the areas. The readers are also recommended to read another upcoming book with a closely related theme and title, i.e. "Autoimmune Disorders – Pathogenic Aspects", edited by Dr Clio Mavragani (ISBN 978-953-308-70-9). I sincerely hope that many of them will find the books useful and inspiring for their future applications in clinical practice and research studies into autoimmunity. Through the editing process, it has been hugely beneficial for me to have the opportunity to learn about the subject in more updated details, and in a systemic way.

I would like to express my sincere gratitude and appreciation to our InTech Publishing Process Manager, Ms Alenka Urbancic, her devoted team, and my associate Dr Susanne Sattler, for their generous support and intellectual input during the editing process. I would also like to thank my family for their constant support and understanding. I dedicate this book respectfully to many of my mentors, particularly Professor Zhong-Ying Shen, Professor Henry HY Wong, Dr Jocelyn W Dow, Dr George BM Lindop, Dr Fiona Miller, Professor Donald Cambell, Professor Laurence C Hunter, Professor David I Stott, Professor Eddy FY Liew, and Professor G Gordon MacPherson. I also acknowledge the generous funding supports received, especially those from the MacFeat Bequest (Glasgow), the Hong Kong Research Grant Committee (Hong Kong), and the Arthritis Research UK (UK). Finally, and specially, I wish to acknowledge the Shantou University Medical College where I received my initial medical education (1977-82), and the Li Ka Shing Academic Foundation which has been generously supporting it, and me in the past.

> **Fang-Ping Huang**  *MBBS, MSc, MUA, PhD* Division of Immunology & Inflammation, Department of Medicine, Imperial College, Hammersmith Hospital, London, UK

XII Preface

(Chapters 12-20), (IV) Pathogenesis & underlying mechanisms (Chapters 21-25), and

The primary aim of this book is to provide most up-to-date information in the 5 defined aspects as stated above, and in the form of Open Access in particular, to be freely available to both clinicians and basic scientists regarding current advances in the areas. The readers are also recommended to read another upcoming book with a closely related theme and title, i.e. "Autoimmune Disorders – Pathogenic Aspects", edited by Dr Clio Mavragani (ISBN 978-953-308-70-9). I sincerely hope that many of them will find the books useful and inspiring for their future applications in clinical practice and research studies into autoimmunity. Through the editing process, it has been hugely beneficial for me to have the opportunity to learn about the subject in

I would like to express my sincere gratitude and appreciation to our InTech Publishing Process Manager, Ms Alenka Urbancic, her devoted team, and my associate Dr Susanne Sattler, for their generous support and intellectual input during the editing process. I would also like to thank my family for their constant support and understanding. I dedicate this book respectfully to many of my mentors, particularly Professor Zhong-Ying Shen, Professor Henry HY Wong, Dr Jocelyn W Dow, Dr George BM Lindop, Dr Fiona Miller, Professor Donald Cambell, Professor Laurence C Hunter, Professor David I Stott, Professor Eddy FY Liew, and Professor G Gordon MacPherson. I also acknowledge the generous funding supports received, especially those from the MacFeat Bequest (Glasgow), the Hong Kong Research Grant Committee (Hong Kong), and the Arthritis Research UK (UK). Finally, and specially, I wish to acknowledge the Shantou University Medical College where I received my initial medical education (1977-82), and the Li Ka Shing Academic Foundation which

> **Fang-Ping Huang**  *MBBS, MSc, MUA, PhD*

> > UK

Division of Immunology & Inflammation, Department of Medicine, Imperial College,

Hammersmith Hospital, London,

(V) Other conceptual advances & new insights (Chapters 26-29).

more updated details, and in a systemic way.

has been generously supporting it, and me in the past.

**Part 1** 

**Disease Phenotypes** 

**Part 1** 

**Disease Phenotypes** 

**1** 

*Italy* 

**Autoimmune Disorders Associated to Type 1** 

*Pediatric Clinic, University of Genoa, IRCCS G. Gaslini Institute, Genoa* 

Giuseppe d'Annunzio and Chiara Russo,

Ramona Tallone and Renata Lorini

**Diabetes Mellitus in Children and Adolescents** 

Autoimmune diseases occur when an individual develops an immune response targeted against specific organ or number of organs. Genetic susceptibility and environmental factors are the main responsible of the development of the autoimmune process leading to a

The majority of organ-specific autoimmune diseases are characterized by an initial infiltration by lymphocytes and macrophages, of the organ, with impaired activity of the organ followed by atrophy. This progressive autoimmune process takes time, and is T cell mediated. Antibodies against specific antigens of the involved gland are detectable in the blood before the clinical onset of the specific disease, so they represent a risk marker and their screening and follow-up allow precocious diagnosis and treatment of autoimmune-

Genetic factors and autoimmunity are closely related since the developmental maturation of T cells occurs through an interaction between HLA antigen and T cell receptor. In genetically susceptible individuals, disease-prone HLA molecules are ineffective at binding and presenting peptides from tissue-specific antigens, therefore auto-reactive T cells can survive and trigger a poorly regulated immune response thereafter (Van den Driessche,

Patients affected by type 1 diabetes mellitus are at increased risk of developing other autoimmune conditions like celiac disease, autoimmune thyroid disease, adrenal

The frequency of organ specific autoimmunity in patients with type 1 diabetes might be due to multiple immunologic abnormalities, i.e an imbalance in B and T lymphocytes, or a tendency to react against specific antigens, or poor ability to develop immune tolerance.

Type 1 diabetes mellitus is the most common endocrinopathy to have clinical onset in childhood or adolescence, with varied pathogenesis, clinical appearance and outcome, and seriously affects patients' and families' life. A combination of genetic, environmental and immunological factors exerts to a T-cell mediated autoimmune process targeted against

insufficiency, atrophic gastritis, autoimmune hepatitis, primary ovarian failure.

insulin-producing -cells in the pancreatic islet of Langerhans (Daneman, 2006).

related disease in genetically susceptible individuals (Allen et al., 2008).

**1. Introduction** 

2009).

clinically evident disease.

**2. Type 1 diabetes mellitus** 

**2.1 Background** 
