Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a case for tissue injury by molecular mimicry

Anti-DNA autoantibodies are the hallmark of human and murine systemic lupus erythematosus (SLE), an autoimmune rheumatic disease of unknown etiology. Some of these antibodies are believed to be pathogenic for kidney tissue an d to initiate immune glomerulonephritis. However, the mechanisms by which a nti-DNA antibodies participate in tissue injury remain controversial. We ha ve studied the in vivo pathogenicity of anti-DNA monoclonal antibodies in i mmune deficient mice, using a panel of murine B cell hybridomas. No consist ent genetic or immunochemical differences were found between pathogenic and non-pathogenic anti-DNA antibodies. However, the two antibody populations differed in their cross-reaction with the acidic actin-binding protein, alp ha -actinin, that is known to play a major role in the structural integrity of glomerular filtration components. These results suggest that kidney dys function in SLE may be facilitated by protein-nucleic acid antigenic mimicr y.