Reactive oxygen species modified polyguanylic acid: immunogenicity and implications for systemic autoimmunity.

The effect of the hydroxyl radical on polyguanylic acid [poly(G)] was investigated with regard to progressive increase of autoantibodies against it in systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Rabbits immunized with both native and ROS-poly(G) induced high titre antibodies. Immune IgG exhibited a high degree of specificity towards the immunogen, reiterated visually by a gel retardation assay. The induced antibodies showed a wide range of cross-reactivity with various synthetic polynucleotides exhibiting B-, A-, and allied conformations. The specificity of induced antibodies resembled the diverse binding characteristics of lupus anti-DNA autoantibodies. Moreover, sera from scleroderma patients showed binding to native and ROS-poly(G). SLE and PSS autoantibodies showed preferential recognition of ROS-poly(G) over native poly(G). These results demonstrate that the hydroxyl modified guanine residues in DNA and RNA can induce circulating SLE and PSS autoantibodies.