Immunopathogenesis of autoimmune endocrine disease for the next generation of experts

View Large Image | Download PowerPoint SlideAn excellent cast of authors, an excellent topic (my bias) and comprehensive coverage of a converging scientific and clinical discipline with basic immunology, immunogenetics, clinical epidemiology, clinical immunology and clinical trials have been assembled in one place and time. The time, as for all comprehensive texts in a rapidly changing field is somewhat delayed. Nevertheless, the synthesis and perspectives of many of the leaders in this field are current enough for those seeking a detailed introduction to organ-specific autoimmunity in a relatively broad sense.Thus, the authors appropriately introduce discussions of non-endocrine immunological disorders, such as therapies for experimental autoimmune encephalitis – an induced animal model of multiple sclerosis. The detail in which animal models of disease are discussed and the emphasis on the details of specific assays make this book most suited to those who will generate the next decade of new information (in particular postdoctoral fellows). There is adequate coverage of clinical disorders and syndromes, but usually not at the level of decision trees and therapeutic algorithms that might be sought by busy house staff or the clinical fellow. An important strength is the presentation of the history of many of the topics covered by those who made a good part of that history. Crucially, the authors have presented a balanced exposition, even pointing out for some when their particular favorite hypothesis is out of favor.Approximately half of the book is appropriately devoted to chapters that cross organ boundaries, and concentrate on introducing basic immunology and concepts such as transgenic models of autoimmunity, islet transplantation in an autoimmune setting, immunotherapy, therapies with peptide antigens, and concepts of tolerance. There is a heavy emphasis on type 1A (immune-mediated) diabetes, with almost none of these basic chapters not devoting a major portion to this disorder. This probably relates to the depth of study of type 1A diabetes with its multiple animal models and what at present must be thousands of investigators. Thus, the coverage of type 1 diabetes at a basic level is as complete as if the text were solely devoted to this topic.The disorders and concepts discussed are linked in many ways. A clinician could take away a very simple but important concept – that these autoimmune disorders cluster in individuals and their families. To varying degrees there are now assays allowing the detection of preclinical disorders and large studies have been completed and are underway in which disease risk (either through genetic – and in particular HLA – typing or through autoantibody testing) is defined years before disease onset.For disorders such as Addison's disease, appropriate early diagnosis can be life saving. For disorders, such as celiac disease, that are strongly associated with type 1 diabetes, the measurement of transglutaminase autoantibodies has simplified screening (e.g. making antigliadin antibodies and antiendomysial antibodies essentially obsolete), but the clinical importance of treating asymptomatic patients is not yet clear. Almost all of the disorders show familial clustering, with monozygotic twins having greater disease risk compared to dizygotic twins, and HLA alleles influencing disease risk. For type 1 diabetes, this increased disease risk (as well as dominant protection by certain alleles) has led to studies in which children are screened in the general population and followed from birth for evidence of autoimmunity and eventually diabetes.The chapters are also related by a lack of effective immunological therapy despite immunopathogenesis. Probably the best therapy is avoidance of gliadine peptides for celiac disease, but even this therapy carries a heavy burden for the individual and the family. It is likely that the promise from basic studies of novel therapies to address autoimmunity is, in part, the genesis of this text with its emphasis on immunopathogenesis. That promise is not fulfilled, in that the first large trials for diabetes prevention (studies mentioned in the text but now with outcomes; e.g. trials of insulin injections or nicotinamide) failed to slow progression to diabetes. With safe and effective therapy for common diseases like hypothyroidism, prevention will probably not be approached for many immune-mediated endocrine disorders until success is achieved for those with grossly inadequate therapy such as patients with type 1 diabetes or Graves' eye disease. The next generation of experts, with a little help from the current generation as encompassed in this text, is thus in great demand by the families who want prevention and cures for this compendium of disorders.