Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR037986-06
Application #
3158367
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-12-01
Project End
1995-05-31
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Connecticut
Department
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Vazquez-Abad, D; Tian, L; Monteon, V et al. (1997) CRI-EM is a human idiotype highly specific for scleroderma. Ann N Y Acad Sci 815:512-5
Vazquez-Abad, D; Tian, L; Zanetti, M et al. (1997) A cross-reactive idiotype in scleroderma. Clin Exp Immunol 108:420-7
Vazquez-Abad, D; Monteon, V; Senecal, J L et al. (1997) Analysis of IgG subclasses of human antitopoisomerase I autoantibodies suggests chronic B cell stimulation. Clin Immunol Immunopathol 84:65-72
Vazquez-Abad, D; Rothfield, N F (1996) Sensitivity and specificity of anti-Jo-1 antibodies in autoimmune diseases with myositis. Arthritis Rheum 39:292-6
Vazquez-Abad, D; Carson, J H; Rothfield, N (1996) Localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells). Cell Tissue Res 286:487-91
Walsh, S J; Algert, C; Rothfield, N F (1996) Racial aspects of comorbidity in systemic lupus erythematosus. Arthritis Care Res 9:509-16
Vazquez-Abad, D; Russell, C A; Cusick, S M et al. (1995) Longitudinal study of anticentromere and antitopoisomerase-I isotypes. Clin Immunol Immunopathol 74:257-70
Senecal, J L; Chartier, S; Rothfield, N (1995) Hypergammaglobulinemic purpura in systemic autoimmune rheumatic diseases: predictive value of anti-Ro(SSA) and anti-La(SSB) antibodies and treatment with indomethacin and hydroxychloroquine. J Rheumatol 22:868-75
Walsh, S J; Algert, C; Gregorio, D I et al. (1995) Divergent racial trends in mortality from systemic lupus erythematosus. J Rheumatol 22:1663-8
Vazquez-Abad, D; Wallace, S; Senecal, J L et al. (1994) Anticentromere autoantibodies. Evaluation of an ELISA using recombinant fusion protein CENP-B as antigen. Arthritis Rheum 37:248-52

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