Summary
Novelty: A monoclonal antibody, denoted DM, directed against the 64 kDa pancreatic beta cell autoantigen, which is associated with the onset of insulin-dependent diabetes mellitus, is disclosed. The isolation of the 64 kDa autoantigen and the generation of anti-idiotype antibodies against MAb DM, are also disclosed. Although the autoimmune basis of IDDM is at present unclear, the 64 kDa autoantigen has been established in the pathogenesis of IDDM. Thus, MAb DM has potential use for the diagnosis of IDDM, and for the prophylaxis and therapy of IDDM. Firstly, MAb DM was used to isolate the 64 kDa autoantigen, potentially useful as the basis for an immunoassay of autoreactive antibodies, which are diagnostic of IDDM. Secondly, the anti-DM anti-idiotypes are potentially useful for the production of both active and passive ‘vaccines’ against IDDM, and as carriers of cytotoxins to effect killing of the autoreative lymphocyte clones.
Biology: The pancreatic beta cell 64 kDa autoantigen target of DM was confirmed by effecting antibody-dependent, complement-mediated cytotoxicity againsed rat insulinoma. The use of 64 kDa autoantigen-based ELISA to detect human sera from IDDM sufferers was also demonstrated; the ELISA detected a proportion of those affected.