DEFICIENT EXPRESSION OF BRUTONS TYROSINE KINASE IN MONOCYTES FROM X-LINKED AGAMMAGLOBULINEMIA AS EVALUATED BY A FLOW CYTOMETRIC ANALYSIS AND ITS CLINICAL-APPLICATION TO CARRIER DETECTION

The B-cell defect in X-linked agammaglobulinemia (XLA) is caused by mu tations in the gene for Bruton's tyrosine kinase (BTK). Using the anti -BTK monoclonal antibody (48-2H), a flow cytometric analysis of intrac ytoplasmic BTK protein expressed in monocytes was successfully perform ed. 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 de ficient expression of the BTK protein in 40 of 41 patients, complete B TK deficiency in 35, and partial BTK deficiency in 5. One patient exhi bited a normal level of BTK expression. All 6 patients with partial BT K deficiency or normal BTK expression had missense BTK mutations. The cellular mosaicism of BTK expression in monocytes from obligate carrie rs 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 a nd limitations in diagnosis of XLA patients and carriers are discussed . (C) 1998 by The American Society of Hematology.