| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
In this study, we investigated the clinical characteristics and the genetic backgrounds of the patients diagnosed as having Mendelian susceptibility to mycobacterial diseases(MSMD) in Japan. Furthermore, we performed analysis of the other genes suspected of association with development of MSMD in the patients without well-known genes.
We performed the genetic analysis on patients diagnosed as having MSMD for the IFNGR1, IFNGR2, IL12B, IL12RB1, STAT1, and NEMO genes. Six patients, 1 patient, and 1 patient had mutations in the IFNGR1, IL12RB1 and NEMO genes, respectively. The proportions of the patients with recurrent mycobacterial infection or multiple osteomyelitis/arthritis were significantly higher in those with the genetic mutations. We also performed the analysis of IRF and CYBB genes newly identified as responsible gene of MSMD. However, none of patients had any mutations in these genes.
Flow cytometric analysis of the expression of IFNγreceptor 1 on CD14-positive cells and IL12 receptorβ1 on T cells and the production of TNF in response to LPS stimulation in CD14-positive cells were performed for the screening for this disease. In addition to these screening, we developed a method to detect the phosphorylation of proteins associated with IFNγ/IL-12 pathway. This method is able to detect the abnormality of the intracellular proteins associated with the elimination of mycobacterium, such as STAT-1, as well as that of molecules on the surface of cells. It is possible that this screening can be useful to detect most of well-known genetic defects rapidly.
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