MOLECULAR IMMUNOLOGICAL STUDIES ON ITRACTABLE UVEITIS FREQUENTLY SEEN IN JAPAN.

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1.Behcet's disease is known to be associated with HLA-B51. In this study, in order to identify new gene (s) related to this disease, we screened the Y109YAC clone containing HLA-B and -C genes and subcloned into pWE15 cosmid vector. As a result, the Y109 YAC clone turned out to be chimeric and about 240 kb are consisting of the chromosome 6 region and remaining 360 kb are consisting of the chromosome 7 region. We have screened the skin fibroblast cDNA library using pM38 cosmid clone as a probe and isolated one cDNA clone. This cDNA clone was recognized to be located on the 1.9kb EcoRl fragment of the pM38 cosmid clone between the MICA and HLA-B genes. Northern hybridization showed approximately 10 kb transcript in the heart, brain, placenta, lung, liver and kidney, and 3kb transcript in the skeletal muscle. Shot-gun sequencing of the cosmid pM56 revealed to be 39,164bp in length and contained as much as 39 Alu-like sequences. Homology search for the up-to date DNA data base showed five regions highly homologous to reported DNAs. Computer analysis of these anonymous genomic sequences reveals the existence of potential coding sequences and the possibility that they are strong candidate genes for determining the pathogenesis of Behcet's disease.2.For the molecular immunological studies of Vogt-Koyanagi-Harada's disease, flowcytometric analysis were done using the aqueous humor lymphocytes and cerebrospinal fluid lymphocytes. It was revealed that memory T cells, as well as activated T lymphocytes were significantly elevated as compared with those in the peripheral blood. Therefore, these cells play main immunological roles in the immunopathogenesis of this disease.3.In conclusion, in this study, molecular immunological mechanisms of the intractable endogenous uveitis syndromes were further investigated. Molecular genetic susceptibility to these diseases, and T cell-mediated immune mechanism possibly lead to the future genetic diagnosis and gene therapy.