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- KINOSHITA Taroh
- Research Institute for Microbial Diseases, Osaka University
Bibliographic Information
- Other Title
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- PNHの分子遺伝学,生化学と生物学
- PNH ノ ブンシ イデンガク,セイカガク ト セイブツガク
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Abstract
<p>Paroxysmal nocturnal hemoglobinuria (PNH) manifests by clonal expansion of mutant hematopoietic stem cells (HSCs) bearing a somatic mutation in the X-linked PIGA gene. PIGA mutations cause defective biosynthesis of GPI and cell surface deficiency of GPI-anchored proteins such as DAF and CD59, leading to intravascular hemolysis and thrombosis. These two major symptoms of PNH can be controlled by eculizumab, an anti-C5 monoclonal antibody. Bone marrow failure, the third major symptom of PNH, is autoimmune-mediated and contributes to the clonal expansion of GPI-defective HSCs by selectively attacking GPI-positive wild-type HSCs. GPI-defective erythrocytes, being protected from intravascular hemolysis by eculizumab, accumulate C3-derived fragments, C3b, iC3b, and C3dg, because of DAF deficiency and in turn become susceptible to CR3-mediated phagocytosis by spleen macrophages. Approximately 3% of Japanese patients with PNH are refractory to eculizumab therapy. Approximately 3% of Japanese people are heterozygous for a single nucleotide polymorphism that changes an amino acid near the eculizumab binding site. New therapeutic measures are needed to solve these issues.</p>
Journal
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- Rinsho Ketsueki
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Rinsho Ketsueki 58 (4), 353-362, 2017
The Japanese Society of Hematology
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Details 詳細情報について
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- CRID
- 1390001205035441152
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- NII Article ID
- 130006882209
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- NII Book ID
- AN00252940
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- ISSN
- 18820824
- 04851439
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- NDL BIB ID
- 028195578
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- PubMed
- 28484166
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed