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Yoshihiko Takeda, M.D.
E-mail:
Research Emphasis:
In sera from patients of systemic rheumatic diseases, autoantibodies against cell components are frequently found. Recently, it has been shown that the target proteins of these autoantibodies play a molecular biologically important role in the cells. My research is focused on the characterization of the autoantigens and the elucidation of the mechanisms of the autoantibody production. We recently found new
autoantibody, designated anti-Pa antibody, which is specific to lupus nephritis. This protein is mainly located in cell nucleus, and binds to RNA with
poly(A)-tail. Therefore this Pa autoantigen is thought to associate with pre-messenger RNA, and might participate in mRNA biogenesis. In order to clarify the molecular biological function of this Pa
autoantigen, we are now mainly working on the characterization of this protein, especially on molecular cloning and analysis of RNA biding properties. We also think that study on autoimmune response against the Pa antigen is important to elucidate the mechanisms of autoantibody production.
Selected Publications:
Hoffman, R. W., Rettenmaier, L. J., Takeda, Y., Hewett, J. E., Pettersson, I., Nyman, U., Luger, A. M., and Sharp, G. C.: Human autoantibodies against the 70kD polypeptide of U1 small nuclear ribonucleoprotein are associated with HLA-DR4 among connective tissue disease patients. Arthritis Rheum. 33, 666-673, 1990.
Takeda, Y., Nyman, U., Winkler, A., S. Wise, K. S., Hoch, S. O., Pettersson, I., Anderson, S. K., Wang, R. J., Wang, G. S., and Gordon C. Sharp, G. C.: Antigenic domains on the U1 small nuclear ribonucleoprotein-associated 70K polypeptide: A comparison of regions selectively recognized by human and mouse autoantibodies and by monoclonal antibodies. Clin. Immunol. Immunopathol. 61, 55-68, 1991.
O'Sullivan, F. X., Ray, C. J., Takeda, Y., Sharp, G. C., and Walker, S. E.: Long-term anti-CD4 treatment of MRL/lpr mice ameliorates immunopathology and lymphoproliferation but fails to suppress rheumatoid factor production. Clin. Immunol. Immunopathol. 61, 421-435, 1991.
Kaneoka, H., Hsu, K.-C., Takeda, Y., Sharp, G. C., and Hoffman, R. W.: Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-U1-70kD autoantibody positive connective tissue disease patients. Arthritis Rheum. 35, 83-94, 1992.
Takeda, Y., Wise, K. S., and Hoffman, R. W.: Nucleotide sequences of immunoglobulin heavy and light chain V-regions from a monoclonal autoantibody specific for a unique set of small nuclear ribonucleoprotein complexes. Nucleic Acids Res. 20, 4099, 1992.
Hoffman, R. W., Cassidy, J. T., Takeda, Y., Smith-Jones, E. I., Wang, G. S., Sharp, G. C.: U1-70-kd autoantibody-positive mixed connective tissue disease in children: A longitudinal clinical and serologic analysis. Arthritis Rheum. 36, 1599-1602, 1993.
Hoffman, R. W., Takeda, Y., Sharp, G. C., Lee, D. R., Hill, D. L., Kaneoka, H., Caldwell, C. W.: Human T cell clones reactive against U-small nuclear ribonucleoprotein autoantigens from connective tissue disease patients and healthy individuals. J. Immunol. 151, 6460-6469, 1993.
Suwa, A., Hirakata, M., Takeda, Y., Jesch, S. A., Mimori, T., Hardin, J. A.: DNA dependent protein kinase (Ku protein-p350 complex) assembles on double stranded DNA. Proc. Natl. Acad. Sci. USA. in press