Anti-DNA Antibodies

Abstract Anti-dsDNA antibodies have been a hallmark of lupus erythematosus for decades, yet their origin remains debated and the mechanisms by which they contribute to disease continue to be investigated. Although many studies have demonstrated they are elicited in an antigen-driven response, others have shown they can also arise from mature autoreactive B cells that become activated by an inflammatory environment. Both direct and indirect mechanisms by which anti-dsDNA antibodies deposit in the kidney and initiate nephritis have been proposed. More recent evidence elucidates mechanisms by which a subset of antibodies cross-reacting with the N-methyl- d -aspartate receptor on neurons may contribute to neuropsychiatric manifestations in lupus. In addition, the internalization of immune complexes of anti-dsDNA antibodies has been demonstrated to activate inflammatory pathways in myeloid cells, thus initiating a feedback loop between innate and adaptive immunity. Overall, this review summarizes insights into the complexity of anti-dsDNA antibodies and the mechanisms by which they exert harm.