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.

R29AI027181

1989-07-01

1994-08-31