The presence of serum antibodies against double stranded (ds) DNA is a characteristic hallmark of patients with systemic lupus erythematosus (SLE). It has become increasingly clear that not only are anti-DNA antibodies an important diagnostic marker for SLE, but that these antibodies also play an…
more important role in disease pathogenesis, particularly in the kidney. It is believed that anti-DNA antibodies are instrumental in lupus nephritis by virtue of binding to a non-DNA kidney protein, the nature of which is unknown. We are interested in two central questions in SLE: 1) What are the mechanisms by which anti-DNA antibodies induce kidney damage in lupus patients? 2) What is the target antigen bound by these antibodies in kidney tissue? Dr. Putterman’s laboratory has confirmed that mesangial cell alpha -actinin is a major cross-reactive target for the anti-dsDNA antibody response in murine and human lupus. In current studies, we are investigating if alpha-actinin can serve not only as a target but also as an antigenic trigger for anti-DNA antibodies, what is the role of differential alpha-actinin expression in the kidney in determining the susceptibility to antibody-induced nephritis, whether anti-alpha-actinin antibodies are associated with specific disease features, and what might be the mechanism by which these and related autoantibodies induce damage in kidney cells. Our goals are to improve our understanding of the pathogenesis of SLE and lupus nephritis, develop novel biomarkers applicable for clinical use, and explore novel targets for therapeutic intervention.
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