Book Review

The Immunology of Human Pregnancy

N Engl J Med 1993; 329:512August 12, 1993

Article

The Immunology of Human Pregnancy
(Contemporary Biomedicine.) by Henry N. Claman. 219 pp., illustrated. Totowa, N.J., Humana Press, 1993. $59.50. ISBN: 0-89603-251-5

The apparent ability of the mammalian fetus to defy the natural law regarding the rejection of foreign tissue has long intrigued scientists. With a few notable exceptions, this fascination has not extended to obstetrician-gynecologists, family doctors, and other health professionals who actually deal with pregnant or infertile women. From my vantage point as an immunologist in a department of obstetrics and gynecology, I see a particularly striking need to educate clinicians about the immunologic aspects of pregnancy and pregnancy loss.

This easily readable, highly focused short book (with six chapters) has an excellent chance of educating clinicians to make informed clinical decisions about patients with pregnancy-related problems. Dr. Claman, a first-rate immunologist with unmatched professional credentials, is uniquely qualified to write such a book. In a very readable style, free from the jargon of immunologists, he critically evaluates the literature on the immunology of pregnancy and recurrent pregnancy loss, highlighting weaknesses and overinterpretations of the data that most of us would miss. The sequence of discoveries leading to the acceptance of such phenomena as blocking antibodies, lymphocytotoxic antibodies, trophoblast-leukocyte cross-reacting (TLX) antigens, and HLA sharing and subsequent studies that shed doubt on their relevance to recurrent pregnancy loss are elucidated and critically evaluated. The result is that the reader starts to question the “facts” quoted over and over again in review articles and begins to acquire a healthy skepticism.

For the most part, the writing is superb. Only rarely did I become bogged down in the intricacies of the HLA system. Fortunately, the most complex immunologic processes are presented in easy-to-follow diagrams. These are a great help in the comprehension of difficult concepts. In addition, there is a summary of the salient points at the end of each chapter. For the reader interested in more detail on a particular subject, each chapter has its own reference section.

The grand finale of this book, and undoubtedly the most relevant clinically, is the last chapter, on the controversy surrounding immunotherapy for women with unexplained recurrent spontaneous abortion. Unlike most authors who review this topic, Claman clearly emphasizes that a woman who has had three successive unexplained spontaneous abortions still has a 50 percent chance that her next pregnancy will proceed to term without any treatment. This clearly is the standard against which trials of immunologic intervention must be judged. Unfortunately, as Claman points out, such has not always been the case. The lack of convincing associations between unexplained recurrent spontaneous abortion and HLA sharing or the presence or absence of blocking antibodies, lymphocytotoxic antibodies, or anti-TLX antibodies is convincingly detailed. Claman astutely points out that perhaps one of the reasons many women with recurrent abortions lack these antibodies is that their pregnancies do not persist to the point at which these antibodies would develop.

The final section deals with Claman's own experience in immunizing 98 women who had had recurrent abortions with their husbands' white cells. The resulting 56 percent rate of successful pregnancy plus the lack of apparent correlation between a successful outcome and the development of blocking factors or lymphocytotoxic antibodies would seem to weaken further the theoretical underpinnings of this treatment. It would have been interesting to know, in the light of these findings, whether Claman continues to use immunotherapy as a treatment for recurrent abortions.

The only suggestion I would make for a second edition of this book would be the inclusion of a chapter on the relation between infection and maternal and fetal immune responses. I suspect that intracellular, genital tract-associated pathogens such as Chlamydia trachomatis, which can persist for years as an asymptomatic chronic infection, would be capable of upsetting the pregnancy-induced regulation of cell-mediated immune responses, leading to expulsion of the fetus. The observation that women with recurrent abortions have an increased incidence of ectopic pregnancies further supports the possible role of chlamydial infections in this problem.

I noticed two typographical errors that, unfortunately, are in key places and caused me some confusion until I realized that they were mistakes. On page 45, “alphadelta receptors” should read “gammadelta receptors.” On page 200, “TSAb” should read “RSAb.” I also learned a new word, “nosological.”

Besides clinicians who deal with women trying to have babies, graduate students, postdoctoral fellows, and medical residents desiring a basic knowledge of pregnancy immunology would find this book a valuable asset. Its honesty and objective critique of the literature would probably render it inappropriate for investigators in the field who are most concerned with self-promotion.

Steven S. Witkin, Ph.D.
Cornell University Medical College, New York, NY 10021