The overall objective of the proposed research is to seek a better understanding of the role of immune processes in the pathogenesis of the chronic rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, vasculitis syndromes, etc.) with the ultimate goal the identification of endogenous or exogenous factors that stimulate the host immune response. Multiple methods of study in numerous laboratories have demonstrated variable levels of immune complexes in patients with the above illnesses but techniques for purification and characterization of the reactants involved have not been sufficient to establish the immunochemical specificities of the relevant antigens and antibodies. New methods have been developed in the applicant's laboratory for the isolation of immune complexes which utilize Staph A receptors for IgC on killed Staphylococcus aureus. Preliminary studies (described below) of this system employing complexes of known composition have been promising. Methods applied included: 1) bulk absorption, then elution of immune complexes for physicochemical study and 2) surface labelling of trace amounts of complexes after Staph A absorption, followed by analytical study of recovered complexes. The latter technique will be particularly applicable to some clinical materials that are limited in volume or concentration, i.e., extracts of tissues, products derived from cultured tissues, cerebrospinal fluid, etc. Techniques will be monitored and refined using complexes of known specificity in order to establish optimum efficiency of recovery and preservation of nativity of immune reactants. Materials for study will be obtained from patients with rheumatic syndromes, where immunogenic stimuli are not known, and from patients with a variety of illnesses associated with immune complex formation where the etiological factors are known, e.g., infective endocarditis, HB hypatitis viral syndromes, etc.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM014627-15
Application #
3150919
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1975-06-30
Project End
1988-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
15
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Hospital for Special Surgery
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10021
Elkon, K B; Bonfa, E; Llovet, R et al. (1989) Association between anti-Sm and anti-ribosomal P protein autoantibodies in human systemic lupus erythematosus and MRL/lpr mice. J Immunol 143:1549-54
Magsaam, J; Gharavi, A E; Parnassa, A P et al. (1989) Quantification of lupus anti-ribosome P antibodies using a recombinant P2 fusion protein and determination of the predicted amino acid sequence of the autoantigen in patients' mononuclear cells. Clin Exp Immunol 76:165-71
Gharavi, A E; Mellors, R C; Elkon, K B (1989) IgG anti-cardiolipin antibodies in murine lupus. Clin Exp Immunol 78:233-8
Bonfa, E; Parnassa, A P; Rhoads, D D et al. (1989) Antiribosomal S10 antibodies in humans and MRL/lpr mice with systemic lupus erythematosus. Arthritis Rheum 32:1252-61
Chu, J L; Gharavi, A E; Elkon, K B (1988) Cryoglobulinemia: analysis of isotype, idiotype and antibody activity by composite gel electrophoresis and immunoblotting. Electrophoresis 9:121-5
Gharavi, A E; Harris, E N; Lockshin, M D et al. (1988) IgG subclass and light chain distribution of anticardiolipin and anti-DNA antibodies in systemic lupus erythematosus. Ann Rheum Dis 47:286-90
Gharavi, A E; Chu, J L; Elkon, K B (1988) Autoantibodies to intracellular proteins in human systemic lupus erythematosus are not due to random polyclonal B cell activation. Arthritis Rheum 31:1337-45
Lockshin, M D; Bonfa, E; Elkon, K et al. (1988) Neonatal lupus risk to newborns of mothers with systemic lupus erythematosus. Arthritis Rheum 31:697-701
Bonfa, E; Bystryn, J C; Elkon, K B (1988) Detection of immunoglobulin G antibodies in melanoma sera reactive with intracellular proteins. J Invest Dermatol 90:207-12
Elkon, K; Bonfa, E; Llovet, R et al. (1988) Properties of the ribosomal P2 protein autoantigen are similar to those of foreign protein antigens. Proc Natl Acad Sci U S A 85:5186-9

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