Double-Stranded DNA Antibodies in Systemic Autoimmunity
(September 2002)
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Double_Stranded DNA Antibodies in Systemic Autoimmunity.pdf)
Systemic lupus erythematosus (SLE) and related systemic autoimmune conditions are diagnosed on the basis of characteristic clinical findings, including inflammatory small joint polyarthropathy, photosensitive rash, and occasionally internal organ involvement, in combination with positive antibodies to a range of cellular antigens.
Antinuclear antibodies (ANA) are detected in around 90 – 95% of such patients, with a homogeneous pattern of nuclear staining classically being associated with antibodies to double-stranded DNA (dsDNA).
Three autoantibodies display a high specificity (> 95%) for SLE:
- Sm: an antibody to "extractable nuclear antigens" (ENA)
- Ribo-P: an antibody to ribosomal phosphoproteins
- dsDNA: an antibody to deoxyribonucleic acid (DNA)
In patients suspected of having SLE, ANA screening alone may miss between 5 - 10% of patients with these conditions, and a full lupus screen incorporating ANA plus ENA, DNA and Ribo-P should be used in this setting.
In addition to assisting in the confirmation of a lupus diagnosis, dsDNA antibodies may be used for other purposes:
- In selected patients, dsDNA levels may parallel disease activity. This is not the case in all individuals, with some patients displaying clinical flares despite stable dsDNA levels, and others displaying clinical quiescence despite high dsDNA results. The incorporation of dsDNA results into decision protocols for immunosuppressive and other management strategies should therefore be approached with caution.
- However, dsDNA antibodies have prognostic significance. The risk of renal disease in patients with positive dsDNA antibodies is increased, with levels > 50 IU/mL associated with approximately twice the background risk for lupus nephritis.
Interpretation of Laboratory Results
dsDNA can be assayed with two major methods: enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). Testing by RIA has high specificity for SLE. However, ELISA testing is more convenient, safer, and provides faster results, but some false positives occur, resulting in lower specificity of this method for lupus.
To circumvent this problem, HAPS Immunology have incorporated a two-tier dsDNA testing strategy:
- Screen with ELISA: If negative, the result will be reported as negative and no further testing will be undertaken.
- If ELISA positive: The results will be confirmed with the more specific RIA test. The RIA result will be reported.
This screening approach has been validated by HAPS Immunology to ensure that dsDNA testing maintains the high specificity for lupus that is so critical in many clinical situations. Around 10 – 15% of dsDNA screens yield positive results on ELISA, so the number of patients requiring RIA confirmation is substantially reduced, hence improving overall test turn-around times.
Normal Range
Normal dsDNA levels are < 7 IU/mL.
Specimen Requirements
A minimum of 1 mL of serum is required. Plasma is not suitable for this assay.
References
- Peter JB, Shoenfeld Y, editors. Autoantibodies. Elsevier, Amsterdam, 1996
- Swaak AJ et al. Arthritis Rheum 1979;22:226-235
- Reeves, G. "Ribosomal-P Antibodies", HAPS Communique, Issue 4, 2002
About the Author
Dr Glenn Reeves, HAPS Immunology wrote this HAPS Communique. If you have any questions regarding this topic the Immunology staff would be happy to assist you on: Telephone: (02) 49214000, Facsimile: (02) 49214400
Immunology Contacts
Dr Glenn Reeves - Staff Specialist - 49214000
Professor Robert Clancy - Staff Specialist - 49236135
Immunology Laboratory - 49214000