Anti-DNA autoantibodies are found in the sera of patients with a variety of autoimmune diseases, including systemic lupus erythematosus. The presence of anti-double stranded DNA autoantibodies is one of the hallmarks of the disease and anti- DNA antibodies are involved in the formation of immune deposits during lupus nephritis. Nevertheless, the mechanisms triggering the production of anti-DNA autoantibodies are not yet understood. Activation by foreign antigens or by anti-idiotypic antibodies are among the hypothesis proposed to explain the emergence of such autoreactive clones. We will test these hypothesis by inducing in normal mice the production of anti-DNA autoantibodies after stimulation with a protein antigen (lysozyme) or anti-idiotypic antibodies against antibodies cross-reacting with lysozyme of DNA. Our approach is based on preliminary results showing possible cross-reactivities between monoclonal anti- lysozyme and anti-DNA antibodies. In a different set of experiments, we will explore the possibility of direct idiotypic interactions between anti-DNA and anti-histone H1 antibodies. The existence of such idiotypic interactions could lead to the formation of pathogenic immune complexes. The monoclonal autoantibodies obtained in our study will be further characterized with respect to their immunochemical properties, pathogenic role and nucleotide sequences.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI026665-05
Application #
3454751
Study Section
Special Emphasis Panel (SSS (C))
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Center for Molecular Medicine/Immunology
Department
Type
DUNS #
City
Belleville
State
NJ
Country
United States
Zip Code
07950