The serological hallmark of the altered immunological status of patients with systemic lupus erythematosus (SLE) is the presence of antibodies in the sera of these patients to variety of autoantigens, most notably DNA and complexes of DNA-histone. Our laboratory has engaged in a study of immune responses in SLE patients to a family of antigens which do not contain DNA but are small RNA protein particles. Precipitating antibodies to one or more of these antigens occur in 80% of unselected SLE patients. All of these antigens have been purified to chemical homogeneity by affinity chromatography methods and sensitive ELISA techniques adapted to measurement of specific antibodies. This proposal aims to study several aspects of the immune response to these RNAprotein antigens as well as some studies of idiotypes on anti-DNA molecules in SLE patients. The problems to be studied are (1) an analysis of the cellular basis of the association of the response to the antigen pairs Ro/SSA, La/SSB and nRNP, Sm. (2) Examination of anti-Ro/SSA antibodies from different SLE subsets for the presence of distinguishing molecular characteristics, including specific idiotype markers. (3) Search for evidence of participation of antibodies to the RNAprotein antigens in circulating immune complexes in SLE and Sjogren's patients. (4) Study of shared idiotypes on anti-DNA molecules in SLE sera and the study of autoanti-idiotypes in individual SLE patients studied longitudinally. (5) Age related production of specific autoantibodies in the SLE population. (6) Search for Ro/SSA antigen in neonatal skin and conducting tissue of the heart. Such studies should enhance our understanding of the production of these antibodies, their role in disease expression, and their relationship to the basic defect in immunoregulation characteristic of these patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM031133-04
Application #
3152210
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1981-12-01
Project End
1989-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
McCarty, G A; Harley, J B; Reichlin, M (1993) A distinctive autoantibody profile in black female patients with lupus nephritis. Arthritis Rheum 36:1560-5
Reichlin, M; Harley, J B; Lockshin, M D (1992) Serologic studies of monozygotic twins with systemic lupus erythematosus. Arthritis Rheum 35:457-64
Reichlin, M (1991) Molecular definition of the Ro(SSA) particle(s): a frequent target of autoimmunity in systemic lupus erythematosus and Sjogren's syndrome. Br J Rheumatol 30 Suppl 1:58-62
Reichlin, M; Van Venrooij, W J (1991) Autoantibodies to the URNP particles: relationship to clinical diagnosis and nephritis. Clin Exp Immunol 83:286-90
Itoh, Y; Rader, M D; Reichlin, M (1990) Heterogeneity of the Ro/SSA antigen and autoanti-Ro/SSA response: evidence of the four antigenically distinct forms. Clin Exp Immunol 81:45-51
Rader, M D; Codding, C; Reichlin, M (1989) Differences in the fine specificity of anti-Ro (SS-A) in relation to the presence of other precipitating autoantibodies. Arthritis Rheum 32:1563-71
Wright-Sandor, L G; Reichlin, M; Tobin, S L (1989) Alteration by heat shock and immunological characterization of Drosophila small nuclear ribonucleoproteins. J Cell Biol 108:2007-16
Reichlin, M; Friday, K; Harley, J B (1988) Complete congenital heart block followed by anti-Ro/SSA in adult life. Studies of an informative family. Am J Med 84:339-44
Hamilton, R G; Harley, J B; Bias, W B et al. (1988) Two Ro (SS-A) autoantibody responses in systemic lupus erythematosus. Correlation of HLA-DR/DQ specificities with quantitative expression of Ro (SS-A) autoantibody. Arthritis Rheum 31:496-505
Sestak, A L; Harley, J B; Yoshida, S et al. (1987) Lupus/Sjogren's autoantibody specificities in sera with paraproteins. J Clin Invest 80:138-44

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