Book Review

Textbook of the Autoimmune Diseases

N Engl J Med 2001; 344:694-695March 1, 2001

Article

Textbook of the Autoimmune Diseases
Edited by Robert G. Lahita, with Nicholas Chiorazzi and Westley H. Reeves. 883 pp., illustrated. Philadelphia, Lippincott Williams & Wilkins, 2000. $169. ISBN: 0-7817-1505-9

Immunologic reactivity as a possible cause of disease (immune-mediated tissue injury) was recognized only at the turn of the 20th century. At that time, Ehrlich first introduced the term “horror autotoxicus,” and the tuberculin reaction, anaphylaxis, and allergy were described. The first report on an autoimmune disease, paroxysmal cold hemoglobinuria, was published by Julius Donath and Karl Landsteiner in 1904. But it was not until the second half of the 20th century that research on the detection and analysis of autoantibodies provided useful new possibilities in the diagnosis of autoimmune diseases and that the improved understanding of tolerance and T-cell regulation allowed better insights into their pathogenesis.

The explosion in the past few decades of information on the development and function of the immune system has contributed to our understanding of the mechanisms of autoreactivity. Given the complexity of immune regulation, it is not surprising that our knowledge regarding this finely tuned network and the consequences of its dysregulation is still incomplete. However, this knowledge is crucial not only for a deeper insight into the pathogenesis of autoimmune disease, but also for the evaluation of new therapeutic methods.

As the gap between basic and clinical science is widening dangerously, it is important to provide information on scientific developments to clinicians. The Textbook of the Autoimmune Diseases succeeds in narrowing this gap by including concise reports on the structure and function of the immune system. Complex problems are dealt with in clear language, and the individual chapters — which are relatively short, despite the ever-increasing amount of information — provide the necessary background. The principle that autoimmune T cells, and their elimination by negative selection, are indispensable to the development of the normal immune system is illustrated and helps to explain the difference between autoreactivity, which includes the activity of autoantibodies that may be present without causing injury, and autoimmune disease, which develops when immunologic mechanisms cause organ or systemic inflammation, tissue damage, or both.

“Disposition” was already accepted 300 years ago as an important element of susceptibility of disease; in 1695, Dr. Adam Lebenwaldt observed that certain families were heavily hit by the plague epidemic, with most members dying of the disease, whereas other families who were equally exposed survived with minimal or no disease. New developments in the field of genetics have had an increasing impact on the identification of susceptibility and resistance to disease, and further results derived from the Human Genome Project are expected to deepen our knowledge. The fact that the same genetic haplotype correlates with an unfavorable course of certain infections, such as the human immunodeficiency virus, and the development of type 1 diabetes, a T-cell-dependent autoimmune disease, stresses the importance of immune regulation in both immunity to infection and the development of autoimmune disease. The chapter on genetics covers the assessment of genetic susceptibility in autoimmune diseases and the different methods for the detection of certain genes that may be associated with disease. The chapter on the inbred murine models of autoimmunity illustrates and further explains the molecular basis of several autoimmune manifestations and shows how genetic and functional studies may lead to the development of new strategies in the treatment of autoimmune diseases.

In spite of an ever-increasing number of animal models and extensive research in patients with different forms of autoimmune disease, the pathogenesis of autoimmune diseases has been clarified for only a few conditions. The section of this textbook on pathogenesis provides a nice compendium of known and emerging mechanisms in the development and course of autoimmune diseases. The individual topics are well chosen, and chapters on autoantibodies, immune complexes, cytokines, and the complement system provide comprehensive information in a concise manner. The discussions on molecular mimicry and superantigens provide information about interesting developments and important, but still controversial, aspects of the pathogenesis of autoimmune diseases.

In the clinical part of the book, which includes a large section on organ-specific and systemic autoimmune diseases, highly experienced clinicians and laboratory specialists provide extensive and critical reviews based on the state of the art and shaped by their personal experiences. The large and increasing number of tests for the detection of autoantibodies is well acknowledged, but at the same time, the importance of knowing about the specificity and sensitivity of each test is emphasized. The chapter entitled “How to Interpret Autoimmune Tests” is of the utmost importance, as it describes the strengths and limitations of various screening tests for the diagnosis of certain diseases. Information on the reliability of laboratory testing and on the advantages of certain methods over others will be helpful for differential diagnosis.

The individual chapters covering the various autoimmune diseases are well organized and include much detailed and useful information that will make this textbook a desk reference for physicians. Discussions of epidemiology and clinical presentation are followed by the description of diagnostic procedures, the detection and the role of autoantibodies, and, if available, consensus statements on diagnosis and treatment. The presentation of treatment options is extensive and often includes the mechanisms of action. A separate chapter on future therapy, based on the large body of scientific information presently available, discusses possible therapeutic approaches at various pathophysiologic levels, such as the level of the inductive cell, the level of the regulatory, self-reactive T cell, and the level of the effector cell. Experimental protocols as they are presently applied are critically reviewed, and possible future developments are discussed with great insight.

This textbook provides a new perspective and can be strongly recommended not only for clinicians and students, but also for scientists interested in and working in the field of autoimmune diseases.

Martha M. Eibl, M.D.
Immunologische Tagesklinik, A-1090 Vienna, Austria