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Reactive oxygen species modified polyguanylic acid: immunogenicity and implications for systemic autoimmunity
Journal of Autoimmunity
|October 20, 1998
Summary
Hydroxyl radicals modify polyguanylic acid (poly(G)), inducing autoantibodies in rabbits. These antibodies cross-react with polynucleotides and show similar binding to lupus autoantibodies, suggesting modified guanine residues trigger SLE and PSS autoantibodies.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Autoantibodies play a critical role in systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS).
- The role of modified nucleic acids in autoantibody generation in autoimmune diseases is an area of ongoing research.
Purpose of the Study:
- To investigate the immunogenic potential of hydroxyl radical-modified polyguanylic acid (ROS-poly(G)) in inducing autoantibodies.
- To compare the specificity and cross-reactivity of induced antibodies with autoantibodies found in SLE and PSS patients.
Main Methods:
- Rabbits were immunized with native and ROS-poly(G) to generate antibodies.
- Gel retardation assays were used to assess antibody specificity.
- Sera from SLE and PSS patients were tested for binding to native and ROS-poly(G).
Main Results:
- Immunization with ROS-poly(G) induced high-titer antibodies in rabbits with specific recognition of the immunogen.
- Induced antibodies exhibited cross-reactivity with various polynucleotide conformations, similar to lupus anti-DNA autoantibodies.
- Sera from SLE and PSS patients recognized both native and ROS-poly(G), with a preference for ROS-poly(G).
Conclusions:
- Hydroxyl modification of guanine residues in poly(G) can elicit specific autoantibodies.
- These findings suggest that hydroxyl-modified guanine residues in DNA and RNA may contribute to the induction of circulating autoantibodies in SLE and PSS.