title: Deletions in the ligand for CD40 in X-linked immunoglobulin deficiency with normal or elevated IgM (HIGMX-1).
abstract: Patients with X-linked Ig deficiency with normal or elevated IgM (HIGMX-1) fail to switch from IgM/IgD to other Ig isotypes. Interaction between the B cell antigen CD40 and the CD40 ligand expressed on activated T cells is critical for T cell driven isotype switching. We have reported that T lymphocytes from three unrelated male patients with HIGMX-1 failed to express CD40 ligand on their surface, but the mRNA for CD40 ligand was of an apparently normal size and level. Analysis of CD40 ligand cDNA from two of the patients revealed deletions that alter the reading frame. Patient 1 displayed two mutations: a C-->A transversion at nucleotide 590 and the deletion of an adjacent C nucleotide. The second patient had a 58 bp deletion from nucleotides 289-346. Furthermore, neither patient expressed a protein product detectable by the CD40L mAb, 5c8.
authors.affiliation: Division of Immunology, Children's Hospital, Boston, MA 02115.
authors.forename: N
authors.initials: N
authors.lastname: Ramesh
authors.forename: R
authors.initials: R
authors.lastname: Fuleihan
authors.forename: V
authors.initials: V
authors.lastname: Ramesh
authors.forename: S
authors.initials: S
authors.lastname: Lederman
authors.forename: M J
authors.initials: MJ
authors.lastname: Yellin
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.forename: L
authors.initials: L
authors.lastname: Chess
authors.forename: F S
authors.initials: FS
authors.lastname: Rosen
authors.forename: R S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D023201:CD40 Ligand; D004247:DNA / Q000032:analysis; D017353:Gene Deletion; D008040:Genetic Linkage; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D014960:X Chromosome
chemical_list: D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D004247:DNA