The influence of susceptibility factors on the immune response to DNA.
Susceptibility to autoimmune disease results from genetic factors that determine the pattern of immune responsiveness to self as well as foreign antigens. These factors may influence the immune response to DNA, a complex macromolecule that can induce antibody responses in normal as well as aberrant immunity. In systemic lupus erythematosus, anti-DNA antibodies target conserved sites present on all DNA and appear to arise by a T dependent mechanism. In contrast, in normal humans, anti-DNA antibodies react to non-conserved sites on certain bacterial DNA and have features suggesting induction by a T independent mechanism. The activity of bacterial DNA reflects the presence of base sequence motifs centering on an unmethylated CpG core. Because of susceptibility factors in patients with systemic lupus erythematosus, bacterial DNA may drive a response crossreactive with self DNA instead of a response specific for the foreign antigen.
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