Bruton's tyrosine kinase (Btk), the gene mutated in the human immunodeficiency X-linked agammaglobulinemia, is activated by LPS and is required for LPS-induced TNF production. In this study, we have investigated the role of Btk both in signaling via another TLR (TLR2) and in the production of other proinflammatory cytokines such as IL-1beta, IL-6, and IL-8. Our data show that in X-linked agamma...

X-linked agammaglobulinemia (XLA) is a rare genetic disorder caused by mutations in the Bruton's tyrosine kinase (BTK) gene. These mutations cause defects in early B cell development. A patient with no circulating B cells and low serum immunoglobulin isotypes was studied as were his mother and sister. Monocyte BTK protein expression was evaluated by flow cytometry. The mutation was determined u...

Development of mammalian B-lineage cells is characterized by progression through a series of checkpoints defined primarily by rearrangement and expression of immunoglobulin genes. Progression through these checkpoints is also influenced by stromal cells in the microenvironment of the primary tissues wherein B-cell development occurs, ie, fetal liver and bone marrow and adult bone marrow. This r...

In this report, we describe seven mutations, including a novel single base pair substitution in intron 1, of the Bruton's tyrosine kinase (Btk) gene found in 12 Korean patients with X-linked agammaglobulinemia. Various mutations, including three novel genetic alterations, were discovered using single-strand conformation polymorphism analysis and direct DNA sequencing. The effect of the intron 1...

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 I...

Bacterial lipopolysaccharides (LPS) derived from a variety of organisms effectively induced C consumption in humans, bovines, and porcines with developmental agammaglobulinemia; birds with experimental agammaglobulinemia; and humans with agammaglobulinemia syndromes. This interaction proceeded even in precolostral piglet sera which contained less than 2.5 x 10(-6) mg/ml gamma globulin, and led ...