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Proposals for Classification of the Clinical Stages, Grading of Severity and the Molecular Pathogenesis of Paroxysmal Nocturnal Hemoglobinuria

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Paroxysmal Nocturnal Hemoglobinuria and Related Disorders

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Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder caused by complement-mediated hemolysis of complement-sensitive erythrocytes and bone marrow failure. A glycosylphosphatidylinositol glycan-class A (PIG-A) gene abnormality at the level of hematopoietic precursors is essential for the occurrence of PNH and explains the deficiency of glycosylphosphatidylinositol (GPI)-anchored membrane proteins in various hematopoietic cells from PNH patients which elicits complement-mediated hemolysis. Quantitation of affected cells of various hematopoietic cell lineages by flow cytometry using monoclonal antibodies to GPI-anchored membrane proteins enables classification of the clinical stages and grading of severity of PNH. However, it is not known how an abnormality of the PIG-A gene occurs or how a PNH clone with a PIG-A gene mutation proliferates or is selected in bone marrow, although some hypotheses have been proposed. We found a high frequency of the HLA-DRB1 *1501-DQA1 *0102-DQB1 *0602 haplotype and high expression of the Wilms' tumor gene, WT1, in Japanese primary PNH and aplastic anemia-PNH syndrome patients. These facts suggest that an immune mechanism in an HLA-restricted manner plays an important role in the occurrence of a PNH clone, and that a PNH clone increases or decreases relatively or absolutely through competition between proliferation of WT1-expressing cells and clonal selection against WT1-expressing cells.

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Authors and Affiliations

  1. First Department of Internal Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, Fukushima, 960-1295, Japan

    Tsutomu Shichishima

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  1. Tsutomu Shichishima
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Editors and Affiliations

  1. Division of Hematology, Internal Medicine Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227-8501, Japan

    Mitsuhiro Omine M.D. (Professor) (Professor)

  2. Department of Immunoregulation, Research Institute for Microbial Diseases Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Taroh Kinoshita Ph.D. (Professor) (Professor)

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© 2003 Springer Japan

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Shichishima, T. (2003). Proposals for Classification of the Clinical Stages, Grading of Severity and the Molecular Pathogenesis of Paroxysmal Nocturnal Hemoglobinuria. In: Omine, M., Kinoshita, T. (eds) Paroxysmal Nocturnal Hemoglobinuria and Related Disorders. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67867-0_5

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  • DOI: https://doi.org/10.1007/978-4-431-67867-0_5

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68004-8

  • Online ISBN: 978-4-431-67867-0

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