BRUTONS-TYROSINE-KINASE EXPRESSION AND ACTIVITY IN X-LINKED AGAMMAGLOBULINEMIA (XLA) - THE USE OF PROTEIN-ANALYSIS AS A DIAGNOSTIC INDICATOR OF XLA

Mutations in the Bruton's tyrosine kinase (BTK) gene result in XLA. De spite the large numbers of BTK mutations reported, no correlation can be made between the clinical phenotype and the gene defects. Analysis of Btk protein expression and activity in individuals with XLA was per formed to characterize the relationship between a particular mutation, the resultant Btk protein and the clinical phenotype. Tn most patient s studied, including those with atypical phenotypes, there was complet e absence of protein expression and activity. Furthermore, in two undi agnosed individuals with a clinical phenotype suggestive of XLA, lack of protein expression was used to confirm an abnormality in Btk. These results underline the importance of protein analysis prior to specula ting on protein structure and function based on the gene mutation. Lac k of Btk expression in atypical phenotypes suggests that there is redu ndancy in B lymphocyte signalling such that alternative signalling mol ecules, or mechanisms, can compensate for the lack of Btk. We also sug gest that analysis of Btk expression can be used as an indicator of XL A. These rapid assays may be used to screen a wider spectrum of indivi duals with humoral immunodeficiency in order to characterize fully the extent of Btk deficiency.