title: Decreased immunoglobulin class switching in Nijmegen Breakage syndrome due to the DNA repair defect.
abstract: Nijmegen breakage syndrome (NBS) is a rare chromosomal-instability syndrome associated with defective DNA repair. Approximately 90% of NBS patients are homozygous for a truncating mutation of the NBS1 gene. As development of the immune system relies on recombination, which involves repair of DNA breaks, one might predict that mutations in the NBS1 gene could cause immunodeficiency. We immunologically investigated the world's largest series of NBS patients (n = 74), confirmed immunodeficiency, and found a discrepancy between relatively normal IgM concentrations, and decreased IgG and IgA concentrations. In addition, a significant relation between low IgA and low IgG levels was found. These data are compatible with a defective class switching in NBS and can be explained by a role of the NBS1 protein in DNA repair, signal transduction, cell cycle regulation or apoptosis.
authors.affiliation: Institute of Neurology, University Medical Centre, Nijmegen, The Netherlands. b.vanengelen@CZZOneu.azn.nl
authors.forename: B G
authors.initials: BG
authors.lastname: van Engelen
authors.forename: J A
authors.initials: JA
authors.lastname: Hiel
authors.forename: F J
authors.initials: FJ
authors.lastname: Gabreëls
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: D C
authors.initials: DC
authors.lastname: van Gent
authors.forename: C M
authors.initials: CM
authors.lastname: Weemaes
mesh_terms: D000367:Age Factors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018797:Cell Cycle Proteins / Q000502:physiology*; D025063:Chromosome Disorders / Q000235:genetics* / Q000276:immunology; D004260:DNA Repair / Q000235:genetics* / Q000276:immunology; D006801:Humans; D017098:IgA Deficiency / Q000276:immunology; D017099:IgG Deficiency / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D009687:Nuclear Proteins / Q000009:adverse effects* / Q000235:genetics*; D013577:Syndrome
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins