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.
Faculty of Medicine, A.M.U., Aligarh, 202002, India.
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Garg
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Ali
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology*; D004247:DNA / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D011068:Poly G / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology
D001323:Autoantibodies; D017382:Reactive Oxygen Species; D011068:Poly G; D017665:Hydroxyl Radical; D004247:DNA