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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

HLA class II haplotype and quantitation of WT1 RNA in Japanese patients with paroxysmal nocturnal hemoglobinuria.

It is unclear how a paroxysmal nocturnal hemoglobinuria (PNH) clone expands in bone marrow, although immune mechanisms involving cytotoxic T lymphocytes, autosomal proliferation, and apoptosis resistance have been hypothesized. To clarify aspects of immune mechanisms and proliferation of PNH cells, we investigated HLA-DRB1, -DQA1, and -DQB1 alleles by polymerase chain reaction (PCR)-based genotyping and expression of the Wilms' tumor gene, WT1, by real-time reverse transcriptase-PCR (RT-PCR) in 21 PNH and 21 aplastic anemia (AA) patients. HLA genotyping indicated that the frequency of DRB1*1501, DQA1*0102, and DQB1*0602 alleles in PNH patients and of DQB1*0602 allele in AA patients was significantly higher than in 916 Japanese controls, and that the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype, found in 13 of 21 PNH patients, 5 of 7 AA-PNH syndrome patients, and 7 of 21 AA patients showed significant differences compared with healthy individuals. RT-PCR analysis showed that the mean values of WT1 RNA were 3413, 712, and 334 copies/microg RNA in PNH, AA, and healthy individuals, respectively. The values for PNH patients were significantly higher than for AA patients and healthy volunteers and were correlated with the proportion of CD16b(-) granulocytes. The high frequency of HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype in PNH, including AA-PNH syndrome, and AA patients suggests that linkage exists between the disorders and that immune mechanisms in an HLA-restricted manner play an important role in the pathogenesis of these disorders. In addition, high expression of WT1 RNA in PNH patients is related to a PNH clone, but it remains unclear whether this causes expansion of a PNH clone.[1]


  1. HLA class II haplotype and quantitation of WT1 RNA in Japanese patients with paroxysmal nocturnal hemoglobinuria. Shichishima, T., Okamoto, M., Ikeda, K., Kaneshige, T., Sugiyama, H., Terasawa, T., Osumi, K., Maruyama, Y. Blood (2002) [Pubmed]
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