Bruton's tyrosine kinase is present in normal platelets and its absence identifies patients with X-linked agammaglobulinaemia and carrier females

X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency caused by mutations in the gene coding for Bruton's tyrosine kinase (Btk) and is char acterized by an arrest of B-cell development. We analysed Btk protein expre ssion in platelets using flow cytometry and found that normal platelets exp ress large amounts of Btk. Assessment of affected males from 45 unrelated X LA families revealed that platelets of the majority of the patients (37 out of 45 families) had decreased or absent Btk expression, and that platelets from carrier females of these families had both normal and mutated Btk exp ression, indicating that megakaryocytes in XLA carriers undergo random X-ch romosome inactivation. These observations demonstrate that Btk is not cruci al for maturation of megakaryocytes and the production of platelets. No cor relation between Btk expression in platelets and clinical phenotype was obs erved in this study. Flow cytometric evaluation using platelets is a simple and rapid method to test Btk expression. It may be used as a screening tes t for XLA and for carrier detection, followed, if necessary, by more expens ive mutation analyses.