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Rheumatic diseases: Immunological mechanism and prospects for new therapies.
  1. BARRY BRESNIHAN, St Vincent's University Hospital
  1. Dublin

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    Rheumatic diseases: Immunological mechanism and prospects for new therapies. J S H Gaston, editor. (£50, $85). Cambridge: Cambridge University Press, 1999. ISBN 0 521 59327 1.

    Rheumatology is entering an exciting new era. The rapid expansion in knowledge of the complexities of the immune system as it functions in both health and disease has provided fresh hope to those engaged in the search for effective and safe novel treatment modalities. In particular, the power of current molecular techniques has provided several new inspirational pieces of the pathogenetic jigsaw puzzle, which may in time expose a refreshingly new therapeutic landscape. In this book, Rheumatic diseases: immunological mechanisms and prospects for new therapies, the editor, Professor J S H Gaston, and his collaborators consider a range of expanding topics that are fundamental to understanding the immunopathogenesis of the systemic inflammatory rheumatic diseases. Apart from one chapter, the authors were recruited from the UK and the USA. In just under 300 pages a considerable volume of information is assembled and discussed although, bearing the title in mind, there are some deficiencies and there is a lack of balance: the book is particularly strong on immunological mechanisms but, regrettably, somewhat weaker on prospects for new treatments. For example, there is no discussion of the potential role of gene therapy.

    The declared concept behind the book is to place emerging experimental information on disease pathogenesis in a clinical context and to emphasise the relevance of each conclusion to potential therapeutic innovation. Rheumatoid arthritis is the predominant disease examined but a considerable amount of discussion is also directed towards wider issues relating to inflammatory pathways and autoimmunity. The book, therefore, will appeal to a number of constituencies including clinical rheumatologists, immunologists, some pharmacologists and research scientists working in arthritis, inflammation and autoimmune disease.

    The contents of the book lean heavily toward aspects of T cell biology, which is the primary theme of five chapters. Practising rheumatologists are aware of the disappointments that followed previous attempts at modulating T cell function in rheumatoid arthritis. However, new insights into T cell biology may offer fresh therapeutic opportunities. The mechanisms involved in T cell autoreactivity, T cell cytokine release, the role of CD40 in maintaining immune responses and the relevance of the TH1 and TH2 balance in chronic inflammation and autoimmunity are very well reviewed but the discussion relating to the possible therapeutic implications of these issues is disappointingly inadequate. In contrast, the reviews of lymphocyte antigen receptor signal transduction and, in particular, the potential for manipulating T cell functions through CD28 and CTLA-4 fulfil the editor's stated aspirations more satisfactorily. There are also excellent reviews of the role of MHC antigens, the formation and structure of autoantibodies, the relevance of cell adhesion mechanisms, apoptosis, monokines and complement receptors. In these chapters, some imaginative therapeutic possibilities are elegantly explored.

    Most chapters contain a number of black and white diagrammatic illustrations that considerably enhance the understanding of the more complicated mechanisms. In addition, each chapter is very liberally referenced but because of the logistics of compiling and printing a book of this sort the references end in 1997. Already, since then, the therapeutic potential of modulating IL18 in rheumatic diseases is being considered. Could the publishers have proceeded faster? Nevertheless, the book is informative, relevant, authoritative and very readable. Professor Gaston should be pleased with his accomplishment.

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