Book Review

The Molecular Pathology of Autoimmune Diseases

Autoimmunity: Physiology and Disease

N Engl J Med 1994; 330:1397-1398May 12, 1994

Article

The Molecular Pathology of Autoimmune Diseases
Edited by Constantin A. Bona, Katherine A. Siminovitch, Maurizio Zanetti, and Argyrios N. Theofilopoulos. 795 pp., illustrated. Langhorne, Pa., Harwood Academic, 1993. $175. ISBN: 3-7186-0555-4

Autoimmunity: Physiology and Disease
Edited by Antonio Coutinho and Michel D. Kazatchkine. 459 pp. New York, Wiley-Liss, 1994. $84.95. ISBN: 0-471-59227-7

The skepticism that once prevailed when the topic of autoimmunity came up in a discussion, or when a “so-called” autoimmune disease entered the differential diagnosis, is difficult to appreciate today. The dogma of the time -- an era that began around 1930 and ended, finally, around 1960 -- was that an antibody could not be an autoantibody. This assumption swayed otherwise reasonable people to invent labels like “erythrocyte-coating substances,” even though they knew that those “substances” were antibodies.

“So-called” began disappearing from the beginning of “autoimmune disease” about 35 years ago; one interesting reason for the new attitude was the discovery at the University of Otago in New Zealand that NZB mice -- a black-furred, local, inbred strain -- were dying of autoimmune hemolytic anemia. If it could happen to a mouse, then why not to a human? Soon, ever-lengthening lists of autoantibodies and autoimmune diseases began invading the literature, demanding attention and pulling down outmoded paradigms.

A climactic event was the 1965 international congress on autoimmunity, sponsored by the New York Academy of Sciences and attended by clinicians and laboratory scientists from around the world. There, Ernest Witebsky came to terms with his long-time (but friendly) adversary, William Dameshek, with a good-natured confession before a packed audience: “Bill, you were right!” -- an act of grace with few parallels in academia.

Autoimmunity is now the Cinderella of immunology. Its glass slipper is molecular biology, and transgenic mice draw its coach. Dazzling techniques have opened superhighways in a field that, 10 years ago, was trapped in a cul-de-sac. Now, with a vast, complex, and sometimes contradictory body of evidence, autoimmunity needs a Scripture to consolidate, legitimize, and interpret the literature. The almost simultaneous publication of The Molecular Pathology of Autoimmune Diseases and Autoimmunity: Physiology and Disease gives clinicians and bench scientists an opportunity to see where the field has been, where it is now, and where it is headed. Taken together, these two books make up a Who's Who of autoimmunity from which diligent readers can extract a broad spectrum of facts, opinions, and conjectures.

The Molecular Pathology of Autoimmune Diseases is a huge book; contributions from an international cast of 89 authors from 11 countries occupy almost 800 pages and weigh 5 pounds. It begins with 18 chapters on the cellular and molecular basis of autoimmunity and ends with 23 chapters on 19 autoimmune diseases and related topics. Argyrios Theofilopoulos emphasizes the historical roots of the problem of autoimmunity in his excellent prologue, but there is no introduction to the fundamentals of the immune system. Some authors presume that the reader has a working knowledge of immunology (the chapter on immunoglobulin genes of autoantibodies plunges directly into its topic), whereas others recapitulate the basics (those on cytokines, adhesion molecules, and T-cell antigen-receptor genes are examples). The chapters on autoimmune diseases also lack a uniform point of view. Some nicely summarize the clinical features of the disease under discussion (for example, those on systemic lupus erythematosus and systemic sclerosis), but others will leave the clinical novice puzzled; the chapters on Hashimoto's disease and multiple sclerosis, for example, fail to mention even a single clinical manifestation or to attempt to explain why the disease merits the reader's attention.

This lack of cohesion is an unsettling feature of The Molecular Pathology of Autoimmune Diseases. There is no overall point of view; no cross-references direct the reader to relevant material in another chapter; attempts to highlight important principles and advances are inconsistent; and there is an excess of repetition. I estimate that about 25 percent of the text is redundant. What we have, in reality, is a collection of 41 stand-alone chapters -- some outstanding, some good, some adequate, and a few substandard or out of place. What is missing is the tight editorial control that would have held the many authors to uniform standards of style and excellence; advised them that they were not giving research seminars on their own work; reminded them to recount the historical background of their topic with meticulous care; blue-penciled howlers like “this infamous experiment” (referring to the famous experiment in which William Harrington was infused with plasma from a patient with autoimmune thrombocytopenia); and corrected errors and misunderstandings, such as the confusion between a genetic mosaic and a chimera and the opaque discussion of retinoblastoma as a model of autoimmune diabetes.

I was surprised to find no chapter on the antiphospholipid antibody syndrome (surely one of the hot topics in the field); nothing on drug-induced autoimmune diseases, paraneoplastic syndromes, or monoclonal gammopathies with peripheral neuropathy; and only a bare mention of autoimmune diseases in B-cell lymphomas. And I found the index ludicrous: 2 1/2 pages for a 5-pound book. For this, which detracts substantially from the book's usefulness, the publisher owes us an apology. Constanin Bona's preface stipulates that “the first edition is only a beginning, and each beginning may be imperfect.” My review has been written in that spirit. This book, despite its deficiencies, is the book on autoimmunity.

Autoimmunity: Physiology and Disease is a different kind of book. It is more compact, less inclusive, and less ambitious than The Molecular Pathology of Autoimmune Diseases. Its contents reflect the point of view of the editors, Antonio Coutinho and Michel Kazatchkine, who champion network theories of the immune system and the primacy of innate autoimmunity. It is a mixed bag of speculations, commentaries on specialized topics, and solid scholarly work. The chapters on B-1 (CD5) B cells by Casali, Kasaian, and Haughton, on rheumatoid factor by Chen and Carson, and on Graves' disease by Dwyer belong to the last category.

The two halves of the book -- “Physiological Autoreactivity” and “Autoimmune Disease” -- lack balance. The first part, for example, contains little or nothing on the selection and deletion of B cells and T cells, costimulatory factors, or the role of HLA in autoimmune diseases, and the second part contains little or nothing on systemic lupus erythematosus, autoimmune skin diseases, or autoimmune diseases of blood cells. These deficiencies may account for the limited perspective of the final chapter, “Autoimmunity Tomorrow,” by the book's editors, which has little to draw on in the preceding text. Among the errors in Autoimmunity: Physiology and Disease, one is repeated several times: the editors' assertion that intravenous gamma globulin is efficacious in many kinds of autoimmune diseases -- a claim used to support their network theory of the immune system. There is very little scientifically rigorous evidence to support this contention. Indeed, one of the book's authors, Lefvert, casts a wary eye on the effectiveness of this treatment in her chapter on myasthenia gravis.

Autoimmunity: Physiology and Disease cannot be recommended to beginners. It is a book for advanced students or practitioners of the art, who will savor it, disagree with it, and perhaps even find inspiration in it. The broader-based Molecular Pathology of Autoimmune Diseases, by contrast, could be read with profit by graduate students and postdoctoral fellows. Subspecialty trainees seeking a more comprehensive view than either of these two books provides should look at the fifth edition of Clinical Aspects of Immunology (P.J. Lachman et al., eds. Boston: Blackwell Scientific, 1993), an imposing and encyclopedic three-volume work that covers almost every aspect of the field.

Robert S. Schwartz, M.D.