Book Review

The Autoimmune Diseases

N Engl J Med 2007; 356:430-432January 25, 2007

Article

The Autoimmune Diseases
Fourth edition. Edited by Noel R. Rose and Ian R. Mackay. 1134 pp., illustrated. San Diego, CA, Elsevier Academic Press, 2006. $199.95. ISBN: 978-0-12-595961-2

The renaissance in the study of regulatory T cells, which began in the mid-1990s, has much improved our understanding of the developmental mechanisms of autoimmune diseases. T-cell–mediated suppression of the immune response was recognized more than three decades ago, but phenotypic characterization of regulatory T cells opened the way for detailed studies of their development and function in inflammatory and autoimmune conditions. Regulatory T cells interfere with the generation of effector T-cell function in vivo. They express the gene coding for transcription factor FOXP3. Studies of the FOXP3 gene in mice have indicated that mutations in this gene impair the function of regulatory T cells and may be the cause of an autoimmune disease. The immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome develops in patients with FOXP3 mutations. Resembling what R.A. Good and J.Z. Solomon called “experiments of nature” in a 1956 Pediatrics article, these cases illustrate that mutation in a single gene may be the reason for a fatal autoimmune disease.

Antigen-Stimulated Lymphocytes in a Lymph Node.

This fourth edition of the classic book The Autoimmune Diseases — edited by Noel R. Rose and Ian R. Mackay, widely recognized experts in autoimmunity and its pathophysiological and clinical aspects — arrives nearly a decade after the third edition (1998). The editors have responded to the challenge of the increasing knowledge in immunology. Important emerging questions, especially as they relate to autoimmune diseases, are taken up. This thoughtfully updated new edition takes into consideration important developments in basic and clinical science. The number of contributors has increased, and the list includes high-caliber international experts in immunology and clinical medicine. The section describing underlying immune functions, as well as the specific chapters discussing individual autoimmune diseases, have been substantially enlarged. Color images, duplicating the black-and-white versions that appear within the text, have been added at the end of the book to demonstrate important cellular interactions in the innate and adaptive immune response. These diagrams are supplemented by images showing pathological findings and histological images of selected diseases. It would be nice, however, to have the color images within the respective chapters, next to the relevant text.

The question asked in the previous edition — “What designates an autoimmune disease?” — is answered as follows in this book: it is “a disease in which autoimmunity plays a directly causative or a significantly contributory role.” This simple, succinct definition runs like a thread through the individual chapters of the present edition, with clear, often consensus-supported statements in reference to the individual autoimmune diseases. Evidence-based information enters as a fundamental category.

Section 1 is devoted to the immunologic basis of autoimmunity. The interactions of innate and adaptive immunity, and the importance and limitations of inheritance versus the role of the environment, are concisely presented. The involvement of T cells in autoimmunity is subdivided into several chapters covering type 1 and type 2 helper T cells, and there is also a discussion of the T cell's role in the induction of tolerance. The evolving knowledge of regulatory T cells is dealt with comprehensively, as is the role of B cells. This approach — in which a topic is looked at from different angles — helps to make complicated interactions understandable even to the nonspecialist.

The chapters in section 2, covering more than 80 individual diseases, are well organized and include information about clinical and epidemiologic features, disease-specific mechanisms of autoimmunity, genetic aspects, environmental influences, animal models, markers for diagnosis, and treatment. With type 1 diabetes used as an example, the possibility of prediction of disease is clearly outlined, based on genetic predisposition, appearance of autoreactivity, and loss of organ function.

Classification of disease entities is based on clinical symptoms and laboratory evaluation. The chapter on diagnosis in section 3 extends these discussions with an up-to-date and critical overview, emphasizing the possibilities and limitations of quality-controlled assay systems. Treatment of individual diseases is included in each chapter that discusses specific diseases, whereas a chapter dedicated to emerging therapies points out the limitations of current treatments, describes new possibilities, and makes reference to clinical trials performed, giving readers the chance to broaden their insights into areas of interest.

This book will be a valuable resource to clinicians involved in the diagnosis and treatment of autoimmune diseases, to scientists who want to follow developments in the field, and to all those who enjoyed and appreciated the previous edition.

Martha M. Eibl, M.D.
Immunology Outpatient Clinic and Biomedical Research Institute, A-1090 Vienna, Austria
martha.eibl@meduniwien.ac.at