Advances in X-linked immunodeficiency diseases.

Abstract

The molecular basis for three well-defined X-linked diseases has recently been identified. In X-linked agammaglobulinemia, the gene encoding a novel cytoplasmic tyrosine kinase (btk) expressed by B cells is defective. This B-cell-specific kinase belongs to a new subfamily of tyrosine kinases. The molecular defect in X-linked hyper IgM affects the gene encoding the CD40 ligand (CD40L, gp39) on T cells. This protein binds to its natural receptor, CD40, expressed constitutively by B cells. The ligand-receptor interaction initiates B-cell proliferation and isotype switching. The molecular defect in X-linked severe combined immunodeficiency disease has been assigned to the gene encoding the gamma chain of the interleukin-2 receptor (IL-2R gamma), which is constitutively expressed by T cells and is involved in the formation of high and intermediate affinity IL-2R complexes. IL-2R-gamma is responsible for the failure of X-linked severe combined immunodeficiency disease T and B lymphocytes to respond to IL-2-dependent signals.

• Authors: H D Ochs, A Aruffo
• Journal: Current opinion in pediatrics (Curr Opin Pediatr) Vol. 5 Issue 6 Pg. 684-91 (Dec 1993) ISSN: 1040-8703 [Print] United States
• PMID: 7907259 (Publication Type: Journal Article, Review)

Chemical References

• Immunoglobulin M
• Ligands
• Membrane Glycoproteins
• Receptors, Interleukin-2
• CD40 Ligand
• Protein-Tyrosine Kinases

Topics

• Adult
• Agammaglobulinemia (genetics)
• CD40 Ligand
• Child
• Female
• Genetic Linkage
• Humans
• Immunoglobulin M (analysis)
• Immunologic Deficiency Syndromes (genetics)
• Ligands
• Male
• Membrane Glycoproteins (deficiency)
• Protein-Tyrosine Kinases (deficiency)
• Receptors, Interleukin-2 (deficiency)
• Severe Combined Immunodeficiency (genetics)
• X Chromosome