title: 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.
abstract: The B-cell defect in X-linked agammaglobulinemia (XLA) is caused by mutations in the gene for Bruton's tyrosine kinase (BTK). Using the anti-BTK monoclonal antibody (48-2H), a flow cytometric analysis of intracytoplasmic BTK protein expressed in monocytes was successfully performed. To examine the possible identification of XLA patients and female carriers by this assay, we studied 41 unrelated XLA families with (35) or without (6) known BTK mutations. A flow cytometric assay showed deficient expression of the BTK protein in 40 of 41 patients, complete BTK deficiency in 35, and partial BTK deficiency in 5. One patient exhibited a normal level of BTK expression. All 6 patients with partial BTK deficiency or normal BTK expression had missense BTK mutations. The cellular mosaicism of BTK expression in monocytes from obligate carriers was clearly shown in 35 of 41 families. The results suggested that most BTK mutations in XLA might result in deficient expression of the BTK protein. We conclude that deficient expression of BTK protein can be evaluated by a flow cytometric assay, and the clinical usefulness and limitations in diagnosis of XLA patients and carriers are discussed.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Futatani
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
authors.forename: S
authors.initials: S
authors.lastname: Tsukada
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Kunikata
authors.forename: S
authors.initials: S
authors.lastname: Arai
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Niida
authors.forename: H
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Y
authors.initials: Y
authors.lastname: Sakiyama
authors.forename: T
authors.initials: T
authors.lastname: Iwata
authors.forename: S
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: O
authors.initials: O
authors.lastname: Tatsuzawa
authors.forename: K
authors.initials: K
authors.lastname: Yoshizaki
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000097:blood* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D008040:Genetic Linkage; D006801:Humans; D009000:Monocytes / Q000201:enzymology*; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D014960:X Chromosome
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human