Anti-dsDNA antibodies

Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely performed to detect anti-dsDNA antibodies in diagnostic laboratories.

[1][2] The first evidence for antinuclear antibodies arose in 1948 when Hargraves, Richmond and Morton discovered the LE cell.

[3] These abnormal cells, which are found in the bone marrow of persons who have SLE are categorised as polymorphonuclear leukocytes with phagocytosed whole nuclei.

There is a great deal of evidence supporting the idea that dead or dying cells are one major source of this extracellular DNA.

These include increased levels of soluble Fas and bcl-2 and polymorphisms in the programmed cell death 1 and runt-related transcription factor X1.

In contrast, pathogenic anti-dsDNA antibodies found in SLE are usually of IgG isotype and show high avidity for dsDNA.

[15] One possible mechanism for anti-dsDNA and their role in nephritis is the formation of immune complexes that arise by indirect binding to DNA or nucleosomes that are adhered to the glomerular basement membrane (GBM).

Another mechanism is direct binding of antibodies to GBM antigens such as C1q, nucleosomal proteins, heparin sulphate or laminin, which can initiate an inflammatory response by activating complement.

They can also be internalised by certain molecules on the GBM cells and cause inflammatory cascades, proliferation and alteration of cellular functions.

Anti-TNFα biological therapies, such as adalimumab, infliximab and etanercept, can often induce the production of anti-dsDNA antibodies.

[22][23] A variety of assay formats can be used to detect and quantify anti-dsDNA antibodies but there is no 'gold standard' for diagnostic purposes and the concordance between different assays/methods is low.

This organelle contains a high concentration of circular DNA with no recognisable nuclear antigens, allowing for the reliable detection of anti-dsDNA antibodies.

Processed DNA can contain regions of ssDNA, allowing detection of anti-ssDNA antibodies, which can give false positive results.

EIA detects low and high avidity anti-dsDNA antibodies, increasing its sensitivity and reducing its specificity.

[1] Flow cytometry for the detection of ANA uses multiplexed polystyrene beads coated with multiple autoantigens, such as SSA, SSB, Sm, RNP, Scl-70, Jo-1, dsDNA, centromere B and histone.

[30][31] Similar to the flow cytometry method of ANA detection, the MIA uses wells containing autoantigens and HEp-2 extract coated beads.

The bead sets are coated with specific autoantigens and can be detected individually to allow identification of the particular autoantibody.

[33] As a result of the highly specific nature of antibodies, they can be engineered to target and bind key motifs.