Anti-dsDNA antibodies

Anti-dsDNA antibodies are a group of anti-nuclear antibodies (ANA) the target antigen of which is double stranded DNA. Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely performed to detect anti-dsDNA antibodies in diagnostic laboratories. They are highly diagnostic of systemic lupus erythematosus (SLE) and are implicated in the pathogenesis of lupus nephritis.

The first evidence for antinuclear antibodies arose in 1948 when Hargraves, Richmond and Morton discovered the LE cell. These abnormal cells, which are found in the bone marrow of persons who have SLE are categorised as polymorphonuclear leukocytes with phagocytosed whole nuclei. Subsequently, in 1957, antibodies to dsDNA were the first autoantibodies to be identified in patients with SLE.

Although the exact mechanism of the generation of dsDNA antibodies is still unknown, it is likely that extracellular DNA is one cause of an immune response against dsDNA. There is a great deal of evidence supporting the idea that dead or dying cells are one major source of this extracellular DNA.Apoptosis is the highly organised process of programmed cell death in which the cell degrades the nuclear DNA and signals for phagocytosis. In people with SLE and other autoimmune disorders this process is thought to be defective, causing either an increase in cell death and/or a decrease in the rate of dead cell clearance.

There is a higher rate of apoptosis in people with SLE and various changes in genes and proteins have been implicated in the defects in apoptosis. These include increased levels of soluble Fas and bcl-2 and polymorphisms in the programmed cell death 1 and run-related transcription factor X1.

Blebs on apoptotic cells contain nearly all the autoantigens found in SLE, and phagocytes bind these apoptotic cells and phagocytose them. If this process is defective, these autoantigens can be released into the circulation allowing an immune response. Serum amyloid P component is a protein that is thought to aid in the clearance of chromatin produced by apoptotic cells and deficiencies in this protein have been shown (in mice) to cause spontaneous formation of ANA. Autoantigens present on the blebs of apoptotic cells are also prone to modification, which can increase their immunogenicity.

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