Deficient Expression of Bruton's Tyrosine Kinase in Monocytes from X-Linked Agammaglobulinemia as Evaluated by a Flow Cytometric Analysis and its Clinical Application to Carrier Detection

Background: The B-cell defect in X-linked agammaglobulinemia (XLA) is caused by mutations in the gene for Bruton's tyrosine kinase (BTK). BTK mutations result in deficient expression of BTK protein in peripheral blood monocytes. Methods: Using the anti-BTK monoclonal antibody (48-2H), a flow cytometric analysis of intra cytoplasmic BTK protein expression in monocytes was performed to identify Iranian patients with XLA phenotype. To examine the possible identification of XLA patients and female carriers by this assay, we studied 13 XLA families. Results: The flow cytometric assay showed deficient expression of the BTK protein in 12 (92%) families. One patient exhibited a normal level of BTK expression. The cellular mosaicism of BTK expression in monocytes from obligate carriers was clearly shown in 9 of 12 (75%) families. Conclusion: The results suggested that most XLA patients have deficient expression of the BTK protein; therefore we conclude that deficient expression of BTK protein can be evaluated by a flow cytometric assay.