Certain """"""""autoimmune"""""""" diseases are observed in women who have undergone breast augmentation procedures with encapsulated silicone gel implants. It has, however, not been determined whether this is a cause and effect relationship or whether the auto immune diseases are found in normally expected incidence and prevalence as in the general population. Our own initial studies have shown that antinuclear antibodies are present in up to 90% of women with silicone breast implants who have defined auto immune diseases and that some of the autoantibodies are those which have been recognized in idiopathic forms of scleroderma and lupus while many others remain unidentified. The objective of this proposal is to comprehensively characterize the profiles and fine specificities of autoantibodies in the sera of patients with silicone breast implants. This will be done with techniques which include immunofluorescence microscopy, Western blotting and immunoprecipitation of biosynthetically labelled cells by which antigenic proteins and/or their associated RNAs can be detected. It has already been shown that there are some new antigens reacting with antibodies from patients with silicone breast implants. A number of sera which recognize unknown antigens will be selected as cloning reagents to probe cDNA expression libraries. Analysis of the nucleic acid and protein sequences of the isolated antigens will be used to determine if characteristic structural and functional motifs are present in these antigens since this information might provide leads to their nature. Recombinant antigens will be generated from the cDNA clones and the authenticity of the recombinant proteins verified in ELISA with the original sera used for library screening. It will then be possible with ELISA and screening of large numbers of sera to ascertain whether autoantibodies to these antigens are unique for silicone-associated auto immune diseases or are also present in the idiopathic diseases. If autoantibody profiles and fine specificities are not different from spontaneous autoimmune diseases, the evidence would favor an adjuvant-like effect of silicone in the promotion of what has been called idiopathic autoimmune disease. However, if the profiles and specificities show that although there are certain similarities as has been reported, there are also distinct differences, the evidence would argue that silicone was provoking autoimmune syndromes by additionally different mechanisms from the idiopathic forms of these diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI034594-01
Application #
3149489
Study Section
Experimental Immunology Study Section (EI)
Project Start
1993-09-01
Project End
1996-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Tan, E M; Ochs, R L; Kumagai, Y et al. (1996) Re-evaluation of autoantibodies and clinical overview of silicone-related disorders. Curr Top Microbiol Immunol 210:291-8