Abstract

Dermatomyositis (DM) and polymyositis (PM) are related autoimmune inflammatory myopathies, but there are significant clinical, pathological and immunological differences. While both PM and DM have been associated with autoantibodies, some are associated predominantly with the PM form, such as anti-Jo-1, antibodies to other aminoacyl-tRNA synthetases, and antibody to the signal recognition particle. DM antibodies are less well characterized, and only one antibody is predominantly associated with the DM form (anti-Mi-2). Little is known about the Mi-2 antigen. In this project, the Mi-2 antigen will be characterized in greater detail. Its structure will be studied and its antigenic components defined using immunoprecipitation, Western blot, and purification with affinity chromatography and fast protein liquid chromatography. ELISA and other techniques will be used to study its tissue and species distribution. The effects of anti-Mi-2 on functional assays, including transcriptional and translational assays will be studied to evaluate the role of Mi-2 in the cell. We will further analyze the antigen by cloning and sequencing the gene for Mi-2. This can predict certain properties, identify structures, or uncover homologies that could help to determine its function or significance. Better definition, characterization, and purification of the Mi-2 antigen will lead to better tests for anti-Mi-2, increasing the value of the test in diagnosis. Study of Mi-2 and anti-Mi-2 may lead to a better understanding of DM and of the reasons for the production of the autoantibodies, which are likely to be related to the underlying etiologic mechanisms.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI027181-05
Application #
3454921
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1989-07-01
Project End
1994-08-31
Budget Start
1993-07-01
Budget End
1994-08-31
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104

  Publications

Arnett, F C; Targoff, I N; Mimori, T et al. (1996) Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis. Arthritis Rheum 39:1507-18
Friedman, A W; Targoff, I N; Arnett, F C (1996) Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis. Semin Arthritis Rheum 26:459-67
Ge, Q; Nilasena, D S; O'Brien, C A et al. (1995) Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen. J Clin Invest 96:1730-7
Kaufman, L D; Varga, J; Gomez-Reino, J J et al. (1995) Autoantibodies in sera from patients with L-tryptophan-associated eosinophilia-myalgia syndrome. Demonstration of unique antigen-antibody specificities. Clin Immunol Immunopathol 76:115-9
Nilasena, D S; Trieu, E P; Targoff, I N (1995) Analysis of the Mi-2 autoantigen of dermatomyositis. Arthritis Rheum 38:123-8
Rider, L G; Miller, F W; Targoff, I N et al. (1994) A broadened spectrum of juvenile myositis. Myositis-specific autoantibodies in children. Arthritis Rheum 37:1534-8
Targoff, I N (1994) Immune manifestations of inflammatory muscle disease. Rheum Dis Clin North Am 20:857-80
Ge, Q; Trieu, E P; Targoff, I N (1994) Primary structure and functional expression of human Glycyl-tRNA synthetase, an autoantigen in myositis. J Biol Chem 269:28790-7
Ge, Q; Wu, Y; Trieu, E P et al. (1994) Analysis of the specificity of anti-PM-Scl autoantibodies. Arthritis Rheum 37:1445-52
Joffe, M M; Love, L A; Leff, R L et al. (1993) Drug therapy of the idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy. Am J Med 94:379-87

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