Abstract

Anticentromere antibodies (ACA) present in sera from patients with CREST or Raynaud's phenomenon with or without a connective tissue disease or in Raynaud's disease have been found to react with 3 centromeric proteins (CENPs): CENP-A, CENP-B and CENP-C. CENP-B which appears to be the major autoantigen has been cloned and is expressed in E. coli. Anti-Scl-70 has been shown to react with topoisomerase I which has also been cloned. Using immunoblotting technique, anti-toposomerase I can be demonstrated in sera negative for anti-SCL-70 on immunodiffusion. Preliminary data suggests that the presence of anti-topoisomerase I may predict the development of scleroderma and that anti-CENP-B may predict the development of CREST syndrome. The presence of antibodies to the 3 centromeric proteins and topoisomerase I will be studied by immunoblotting with chromosomes. The level of anti-CENP-B and topoisomerase I will be studied by ELISA assay using the fusion protein CENP-B and topoisomerase I. We postulate that there is a common genetic background in patients with these autoantibodies which can be demonstrated by looking for the presence of cross reactive idiotypes. Affinity purified auto-antibodies to CENP-B and to topoisomerase I and autoantibodies to CENP-B and topoisomerase I generated by human-human hybridomas will be used to produce polyclonal anti-idiotypes in rabbits and monoclonal anti-idiotypes in mice. We will look for cross reactive idiotypes in sera from patients and their relatives. Sera containing cross reactive idiotype will be studied using electrofocusing and labelled antigen to determine whether or not the cross reactive idiotype reacts with antigen. A prospective study of patients with Raynaud's phenomenon unassociated at the onset with a connective tissue disease will be carried out to determine the clinical significance of the presence and amount of anti-CENP-B and topoisomerase I. In addition, the prognostic significance of the presence of anti-CENP-A and anti-CENP-C will be determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR037986-03
Application #
3158365
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-12-01
Project End
1989-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
3
Fiscal Year
1989
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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