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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-3-26
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pubmed:abstractText |
The gene that encodes nuclear factor kappaB (NF-kappaB) essential modulator (or NEMO, also known as IKKgamma) is required for activation of the transcription factor NF-kappaB. We describe mutations in the putative zinc-finger domain of NEMO that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED). These mutations prevent CD40 ligand (CD40L)-mediated degradation of inhibitor of NF-kappaB alpha (IkappaB-alpha) and account for the following observations: B cells from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and antigen-presenting cells (APCs) are unable to synthesize the NF-kappaB-regulated cytokines interleukin 12 (IL-12) or tumor necrosis factor alpha (TNF-alpha) when stimulated with CD40L. Nevertheless, innate immunity is preserved in XHM-ED patients because APCs retain the capacity to respond to stimulation by lipopolysaccharide or Staphylococcus aureus Cowan's antigen (SAC). Overall, the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of CD40-mediated NF-kappaB activation for B cell immunoglobulin class-switching.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1529-2908
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
223-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11224521-Adolescent,
pubmed-meshheading:11224521-Antigen-Presenting Cells,
pubmed-meshheading:11224521-B-Lymphocytes,
pubmed-meshheading:11224521-Child,
pubmed-meshheading:11224521-Cytokines,
pubmed-meshheading:11224521-Ectodermal Dysplasia,
pubmed-meshheading:11224521-Genetic Linkage,
pubmed-meshheading:11224521-Humans,
pubmed-meshheading:11224521-Hypergammaglobulinemia,
pubmed-meshheading:11224521-I-kappa B Kinase,
pubmed-meshheading:11224521-Immunoglobulin M,
pubmed-meshheading:11224521-Immunoglobulins,
pubmed-meshheading:11224521-Male,
pubmed-meshheading:11224521-Mutation, Missense,
pubmed-meshheading:11224521-NF-kappa B,
pubmed-meshheading:11224521-Pedigree,
pubmed-meshheading:11224521-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11224521-T-Lymphocytes,
pubmed-meshheading:11224521-X Chromosome
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pubmed:year |
2001
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pubmed:articleTitle |
Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia.
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pubmed:affiliation |
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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