| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
Vogt-Koyanagi-Harada disease (VKH) may be caused by autoimmune responses against melanocytes in various tissues. Since the mechanism for development of VKH has not been clear yet, we attempted to identify the autoantigens. To identify antigens, we used sera that might contain specific antibodies for the VKH antigens. Although Western blot analysis did not show VKH specific bands, by immunoprecipitation analysis, a 46 kDa band was observed in melanoma cells, Skme123, but not in K562 cells, with sera from VKH, but not with sera from healthy individual, suggesting that this protein may be associated with VKH. An expression cDNA library from Skme123 was screened with sera from 7 VKH, and 26 genes were isolated. However, melanocyte specific antigen was not identified. The cDNA clones obtained with sera from 2 patients were identified to be lens epithelium derived growth factor. The antibody for this protein was detected in 4 of 12 VKH and 3 of 6 healthy individuals, suggesting that this protein might not be associated with VKH. Increased mononuclear cells in cerebrospinal fluid may contain T cells reacted to melanocytes in choroid plexus of brain. We cloned T cells from cerebrospinal fluid of VKH. The T cell clones recognized proteins from melanocytes and melanoma, but not those from nonmelanocytic cells. This reaction was blocked by anti-DR antibody, and the significant association of VKH with HLA-DRB*0405 and DQB1*0401 was reported. Therefore, these results suggested that HLA-DR restricted CD4+ T cells specific for melanocytes may be involved in the development of VKH.
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