MOLECULAR AND CELLULAR ASPECTS OF X-LINKED AGAMMAGLOBULINEMIA

The chapter discusses the current knowledge in the field of X-Linked Agammaglobulinemia (XLA) in the context of the recent developments. XLA, by being the first human disease caused by a defect in the function of a cytoplasmic tyrosine kinase (PTK)– the XLA product designated Btk (Bruton's agammaglobulinemia tyrosine kinase)– has attracted various investigators with interest in cellular immunology, clinical immunology, genetics, gene therapy, structural biochemistry, and signal transduction. The clinical observations in patients with XLA have been of great importance for the understanding of the role of antibodies in the immune defense. One way of studying these phenomena is to compare various forms of immune deficiencies. Although most manifestations are similar in patients with different immunoglobulin deficiencies there are several examples of those being more as well as less frequent in XLA. It is apparent that the virtual absence of both immunoglobulin and B lymphocytes in the majority of patients distinguishes XLA from most other deficiencies. This defect, as demonstrated by experimental immunizations, results in a typical feature of XLA– namely, the lack of an antibody response and the failure to clear microbial antigens, such as bacteriophage ϕX174. © 1995, Academic Press Inc.