Antigens anti-dsDNA antibodies

Pathogenic anti-dsDNA antibodies from human lupus are different from non-pathogenic anti-dsDNA antibodies from normal people. Results from structural studies reveal that the production of these pathogenic antibodies is antigen-driven and helper T cell-dependent. 

Anti-dsDNA Antibodies Are Antigen-Driven. There is evidence that variable regions of both heavy and light chains of both murine and human monoclonal anti-dsDNA antibodies are produced after an affinity maturation process via isotype switching, clonal selection, and somatic mutation (D5, D9, Wll, C16, V3). These findings suggest that anti-dsDNA antibodies are produced by an... 

Direct evidence of DNA as an antigen source to drive autoantibody production was derived from experiments using combined DNA-protein as an immunogen to immunize mice. The mice immunized with the DNA-peptide complex produce anti-dsDNA antibodies with pathogenic properties (D7). 

Anti-dsDNA antibodies are both specific and pathogenic to SLE. As mentioned previously, these autoantibodies are produced by an antigen-driven mechanism. They are organ-specific, especially kidney. We will discuss the close relationship between anti-dsDNA and lupus nephritis and the proposed mechanism by which anti-dsDNA leads to lupus nephritis. 

Circulating Immune Complex. Anti-dsDNA/DNA immune complexes have long been considered responsible for the development of lupus nephritis. The level of immune complexes in SLE patients with active disease detected by monoclonal anti-DNA antibodies is higher (T7). About half of SLE patients had elevated amounts of DNA antigen in the immune complexes (N4, R2, S27). 

There are several relatively new therapeutic modalities for the treatment of SLE. Trying to eliminate pathogenic anti-dsDNAs, Ferguson etal. developed an antigen-based heteropolymer (AHP) (F3). AHP is a bispecific dsDNA x monoclonal antibody (mAb) complex (dsDNA x anti-CRl mAb) that enables the use of the unique immune complex-binding and clearing capacity of the complement receptor (CR1) on primate erythrocytes. In vitro studies of AHP show a substantial reduction (>90%) of anti-dsDNA titer (F20). In vivo studies in two rhesus monkeys indicate that the erythrocyte-bound antibodies are rapidly cleared from the circulation (F3). 

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