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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-12-25
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pubmed:abstractText |
Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical antibody-mediated autoimmune disease characterized by production of autoantibodies against a variety of autoantigens and immune complex-type tissue inflammation, most prominently in the kidney. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB) mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to search for susceptibility genes for aberrant activation of B1 cells in these mice showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues. Sequence and functional analyses of the gene revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly higher frequency compared with the healthy controls. Our findings suggest that these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form one genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0964-6906
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pubmed:author |
pubmed-author:AbeMasaakiM,
pubmed-author:AtsumiTatsuyaT,
pubmed-author:HiroseSachikoS,
pubmed-author:JiangYiY,
pubmed-author:KatoKiyoshiK,
pubmed-author:KawaiTakakoT,
pubmed-author:KoikeTakaoT,
pubmed-author:MatsuokaShujiS,
pubmed-author:N,
pubmed-author:NakamuraKazuhiroK,
pubmed-author:NishimuraHiroyukiH,
pubmed-author:OhtsujiMarekiM,
pubmed-author:ShiraiToshikazuT,
pubmed-author:TsuruiHiromichiH,
pubmed-author:UenoHirooH
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
171-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:14695357-Adult,
pubmed-meshheading:14695357-Aged,
pubmed-meshheading:14695357-Aged, 80 and over,
pubmed-meshheading:14695357-Amino Acid Sequence,
pubmed-meshheading:14695357-Animals,
pubmed-meshheading:14695357-Antigens, CD5,
pubmed-meshheading:14695357-B-Lymphocytes,
pubmed-meshheading:14695357-Case-Control Studies,
pubmed-meshheading:14695357-Cell Division,
pubmed-meshheading:14695357-Cell Survival,
pubmed-meshheading:14695357-Female,
pubmed-meshheading:14695357-Genetic Predisposition to Disease,
pubmed-meshheading:14695357-Humans,
pubmed-meshheading:14695357-Lupus Erythematosus, Systemic,
pubmed-meshheading:14695357-Lymphocyte Activation,
pubmed-meshheading:14695357-Male,
pubmed-meshheading:14695357-Mice,
pubmed-meshheading:14695357-Mice, Inbred NZB,
pubmed-meshheading:14695357-Middle Aged,
pubmed-meshheading:14695357-Molecular Sequence Data,
pubmed-meshheading:14695357-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:14695357-Polymorphism, Genetic,
pubmed-meshheading:14695357-Quantitative Trait Loci,
pubmed-meshheading:14695357-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:14695357-Sequence Analysis
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pubmed:year |
2004
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pubmed:articleTitle |
Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus.
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pubmed:affiliation |
Second Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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