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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2004-3-4
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pubmed:abstractText |
We found 10 individuals from 7 unrelated families among 170 severe combined immunodeficiency (SCID) patients who exhibited 9 different Janus kinase 3 (JAK3) mutations. These included 3 missense and 2 nonsense mutations, 1 insertion, and 3 deletions. With the exception of 1 individual with persistence of transplacentally transferred maternal lymphocytes, all infants presented with a T-B+NK- phenotype. The patient mutations all resulted in abnormal B-cell Janus kinase 3 (JAK3)-dependent interleukin-2 (IL-2)-induced signal transducer and activator of transcription-5 (STAT5) phosphorylation. Additional analyses of mutations permitting protein expression revealed the N-terminal JH7 (del58A) and JH6 (D169E) domain mutations each inhibited receptor binding and catalytic activity, whereas the G589S JH2 mutation abrogated kinase activity but did not affect c association. Nine of the 10 patients are currently alive from between 4 years and 18 years following stem cell transplantation, with all exhibiting normal T-cell function. Reconstitution of antibody function was noted in only 3 patients. Natural killer (NK) function was severely depressed at presentation in the 4 patients studied, whereas after transplantation the only individuals with normal NK lytic activity were patients 1 and 5. Hence, bone marrow transplantation is an effective means for reconstitution of T-cell immunity in this defect but is less successful for restoration of B-cell and NK cell functions.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Codon, Nonsense,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/JAK3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2009-18
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14615376-B-Lymphocytes,
pubmed-meshheading:14615376-Cell Line, Transformed,
pubmed-meshheading:14615376-Codon, Nonsense,
pubmed-meshheading:14615376-DNA-Binding Proteins,
pubmed-meshheading:14615376-Female,
pubmed-meshheading:14615376-Gene Deletion,
pubmed-meshheading:14615376-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:14615376-Humans,
pubmed-meshheading:14615376-Infant,
pubmed-meshheading:14615376-Interleukin-2,
pubmed-meshheading:14615376-Janus Kinase 3,
pubmed-meshheading:14615376-Killer Cells, Natural,
pubmed-meshheading:14615376-Male,
pubmed-meshheading:14615376-Milk Proteins,
pubmed-meshheading:14615376-Mutation, Missense,
pubmed-meshheading:14615376-Phenotype,
pubmed-meshheading:14615376-Phosphorylation,
pubmed-meshheading:14615376-Protein-Tyrosine Kinases,
pubmed-meshheading:14615376-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:14615376-STAT5 Transcription Factor,
pubmed-meshheading:14615376-Severe Combined Immunodeficiency,
pubmed-meshheading:14615376-Trans-Activators,
pubmed-meshheading:14615376-United States
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pubmed:year |
2004
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pubmed:articleTitle |
Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation.
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pubmed:affiliation |
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. rober060@mc.duke.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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