| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Hiroyuki Human Science and Tecnology Center, Toin University of Yokohama, Professor, 工学部, 教授 (60189313)
TSURUI Hiromichi Dept.Pathol.Juntendo Univ.Sch.Med., Assistant Professor, 医学部, 助手 (40217386)
HIROSE Sachiko Dept.Pathol.Juntendo Univ.Sch.Med., Associate Professor, 医学部, 助教授 (00127127)
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| Budget Amount *help |
¥31,000,000 (Direct Cost: ¥31,000,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1995: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1994: ¥15,200,000 (Direct Cost: ¥15,200,000)
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| Research Abstract |
In SLE,a diversity of disease features in association with a wide spectrum of autoantibodies develops. There are subsets of patients with either antiphospholipid syndrome, autoimmune hemolytic anemia, autoimmune thrombocytopenia and/or even B-cell chronic lymphocytic leukemia (B-CLL). Because SLE is a multigenic disease, diversities of disease features in individual patients are thought to be due to different combinations of disease susceptibility genes contributing to each pathologic condition. This notion is consistent with findings observed in several genetically determined SLE-prone mouse models, in which particular autoantibodies are detected in one, but not in others. Studies indicated that, in addition to disease susceptibility alleles, disease modifiers are also involved in the development of each disease feature. To delineate the underlying genetic basis, we analyzed chromosomal segments containing loci contributing to each SLE feature, using NZB,NZW,(NZB x NZW) F1, (NZW x BXSB) F1, their backcross progeny, congenic strains, and transgenic mice. Results showed that each disease feature was independently controlled by different combinations of two to three, or more, major alleles, in which some were common and some were unique for different features. Gene interactions, in which some functioned in a coordinate manner and some, in an additive manner as a threshold liability model for the disease susceptibility, were suggested. There were several potentially important candidate genes, which may be relevant to each disease feature. We could identify several alleles which regulate aberrant proliferation and/or differentiation of B1, cells, precursors of both pathogenic autoantibody-producing cells and B-CLL.
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