Introduction to Immunodeficiency Reviews
The description of X-linked agammaglobulinaemia (XLA) 48 years ago provided the catalyst for a fruitful interaction between basic immunologists and clinicians, and was the beginning of Clinical Immunology as practised in the UK today. Over the subsequent 40 years many more immunodeficiency syndromes were described and partially characterized at a functional level, but it has been the ability to clone genes in the past decade that has led to a dramatic increase in our understanding at a molecular level of most of these disorders. There are now about 75 characterized single gene defects causing primary immunodeficiency, with about another 20 expected to be discovered in the current decade. Most are associated with a predisposition to infection with either a broad or selective range of organisms, and most affected patients would die from infection without antibiotics. However, a few patients with loss of an apparently crucial protein involved in host defence surprisingly survive into adulthood with only minimal infection, suggesting the presence of unknown back-up systems. Furthermore, complicated clinical phenotypes, with immune dysregulation and autoimmunity, may result from inherited defects allowing partial expression of some of these proteins. 
 
Clinical and Experimental Immunology will be publishing a series of reviews on most of the primary immunodeficiency syndromes over the next 12 months, appropriately leading up to the 50th anniversary of the discovery of XLA. The first of these is the review by Gaspar & Conley on XLA that appeared in the March 2000 issue of the Journal [1]. These reviews will not only highlight the most recent advances in our understanding of the molecular mechanisms of specific disorders, but will also discuss new developments in clinical management. This field has pioneered the correction of disease by bone marrow grafting and gene therapy, and is likely to set the precedent for a complete cure by gene replacement in the next few years.