Anticentromere antibodies (ACA) present in sera from patients with scleroderma, CREST, primary or secondary Raynaud's phenomenon react with 3 centromeric proteins (CENPs): CENP-A, CENP-B, and CENP-C. CENP-B, the major autoantigen, has been cloned and expressed in E. coli. Anti-Scl-70 reacts with topoisomerase I. The antigen has been cloned and, in addition, chemically purified. An ELISA for anti-CENP-B and for anti-Topoisomerase I have been established and are more sensitive than immunoblotting or immunodiffusion. Anti-topoisomerase I predicts the development of tight skin and anti-CENP-B the development of telangiectasias in patients with Primary Raynaud's disease. We have found IgA and IgM anti-topoisomerase I and ACA. The autoantibodies will be studied using the ELISA and immunoblotting. CENP-C and CENP-A will be fully cloned and expressed in bacteria. The epitopes on topoisomerase I, CENP-C, and CENP-A will be mapped to determine whether the autoantibody response is polyclonal as appears to be the case for anti-CENP-B. The anti-topoisomerase response will be studied to determine immunoglobulin class and subclass and to determine whether there is heavy or light chain skewing as found for the anti-CENP-B response. The clinical significance of IgA and IgM ACA and anti-topoisomerase I autoantibodies will be studied in scleroderma and its subsets. """"""""Normal"""""""" anti-topoisomerase I and ACA will be compared with those in disease states. A prospective 5 year study of patients with Raynaud's disease will be carried out to determine the clinical significant of the presence and amount of anti-CENP-B, anti-CENP-A, anti-CENP-C, and anti-topoisomerase I.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR037986-07
Application #
3158368
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-12-01
Project End
1995-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
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