Abstract

This research project is concerned with the study of autoantibodies in the sera of patients with connective tissue diseases. These autoantibodies arise spontaneously in patients with systemic lupus erythematosus, mixed connective tissue disease, Sjogren's syndrome and scleroderma. Many of these antibodies react specifically with non-histone proteins complexed to chromosomes. One of the objectives is to characterize each nuclear antigen-antibody system. Information obtained to date has shown that antibodies to different non-histone proteins are present in different disease conditions. In other words, diseases such as systemic lupus erythematosus or scleroderma have their own characteristic profiles of antibodies to nuclear non-histone proteins. Thus, characterization of the specificities of these antibodies can be used as markers in differential diagnosis. The naturally occurring autoantibodies have also been used as reagents to isolate nuclear non-histone proteins. We have characterized a centromere (kinetochore) antigen with the use of one of these reagent antibodies. Work in progress is currently concerned with the isolation and characterization of other non-histone chromosomal proteins which react with autoimmune antibodies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR032063-05
Application #
3156175
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1983-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037

  Publications

Ochs, R L; Muro, Y; Si, Y et al. (2000) Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. J Allergy Clin Immunol 105:1211-20
Pollard, K M; Pearson, D L; Bluthner, M et al. (2000) Proteolytic cleavage of a self-antigen following xenobiotic-induced cell death produces a fragment with novel immunogenic properties. J Immunol 165:2263-70
Zhang, J Y; Chan, E K; Peng, X X et al. (1999) A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma. J Exp Med 189:1101-10
Erlanson, M; Casiano, C A; Tan, E M et al. (1999) Immunohistochemical analysis of the proliferation associated nuclear antigen CENP-F in non-Hodgkin's lymphoma. Mod Pathol 12:69-74
Furuta, K; Hildebrandt, B; Matsuoka, S et al. (1998) Immunological characterization of heterochromatin protein p25beta autoantibodies and relationship with centromere autoantibodies and pulmonary fibrosis in systemic scleroderma. J Mol Med 76:54-60
Covini, G; von Muhlen, C A; Pacchetti, S et al. (1997) Diversity of antinuclear antibody responses in hepatocellular carcinoma. J Hepatol 26:1255-65
Furuta, K; Chan, E K; Kiyosawa, K et al. (1997) Heterochromatin protein HP1Hsbeta (p25beta) and its localization with centromeres in mitosis. Chromosoma 106:11-9
Pollard, K M; Lee, D K; Casiano, C A et al. (1997) The autoimmunity-inducing xenobiotic mercury interacts with the autoantigen fibrillarin and modifies its molecular and antigenic properties. J Immunol 158:3521-8
Andrade, L E; Chan, E K; Peebles, C L et al. (1996) Two major autoantigen-antibody systems of the mitotic spindle apparatus. Arthritis Rheum 39:1643-53
Casiano, C A; Tan, E M (1996) Antinuclear autoantibodies: probes for defining proteolytic events associated with apoptosis. Mol Biol Rep 23:211-6

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