Analysis of Bruton’s Tyrosine Kinase Deficiency in Patients with Presumed X-Linked Agammaglobulinemia

Abstract

X-linked agammaglobulinemia (XLA) is a fully penetrant X-linked recessive disorder characterized by the early onset of recurrent bacterial infections, profound hypogammaglobulinemia and a marked decrease in the number of B-lymphocytes [1]. The gene defective in XLA has been identified as a non-receptor proteine tyrosine kinase, BTK (Bruton´s tyrosine kinase) [2,3]. Over 600 mutations have been described in the BTK gene and they are spreaded throughout the gene [4]. Mutational analysis has revealed that there is considerable heterogeneity in the clinical spectrum of XLA, with atypical individuals having small numbers of mature B lymphocytes and some immnoglobulin production [5]. Analysis of Btk protein expression in primary cells of XLA patients has shown that the large majority of individuals do not express protein regardless of their mutation [6]. As it is yet known Btk is expressed not only in B cells but also in granulocytes and monocytes. In the present work we applied a flow cytometric test employing whole blood to detect Btk expression in monocytes to identify XLA patients.