Antibodies to double-stranded (ds)DNA, Sm, and U1 RNP
- Donald B Bloch, MD
Donald B Bloch, MD
- Associate Professor of Medicine
- Harvard Medical School
Selected antinuclear antibodies (ANAs), including anti-double-stranded deoxyribonucleic acid (dsDNA) and anti-Sm, are highly specific for the diagnosis of systemic lupus erythematosus (SLE). Antibodies directed against the U1 ribonucleoprotein (RNP) complex are markers for mixed connective tissue disease (MCTD) and may be seen in patients with SLE and other disorders. (See "Diagnosis and differential diagnosis of systemic lupus erythematosus in adults" and "Definition and diagnosis of mixed connective tissue disease".)
The sensitivity of anti-dsDNA, anti-Sm, and anti-U1 RNP antibodies for the diagnosis of SLE is relatively low, but the specificity of anti-dsDNA and anti-Sm antibodies for SLE makes them invaluable tools to assist in the diagnosis of this disease.
This topic will review the clinical significance of anti-dsDNA, anti-Sm, and anti-U1 RNP autoantibodies. The clinical significance of antiribosomal P autoantibodies, which are also highly specific for the diagnosis of SLE, and of other antinuclear antibodies is discussed separately. (See "Antiribosomal P protein antibodies" and "Measurement and clinical significance of antinuclear antibodies" and "Miscellaneous antinuclear antibodies".)
Antibodies to deoxyribonucleic acid (DNA) can be primarily divided into two groups: those reactive with denatured, single-stranded (ss)DNA and those recognizing native, double-stranded (ds)DNA . Autoantibodies to DNA were first described in the 1950s. Their binding to cell nuclei, using a Hep-2 cell line substrate, for example, may be visualized by indirect immunofluorescent (IIF) staining (picture 1). (See 'Anti-ssDNA antibodies' below and 'Anti-dsDNA antibodies' below.)
Anti-ssDNA antibodies — Anti-ssDNA antibodies are generally not useful in the diagnosis and management of systemic lupus erythematosus (SLE). Antibodies that identify ssDNA react primarily with the purine and pyrimidine bases that are buried within the beta helix of double-stranded deoxyribonucleic acid (dsDNA) . Because these epitopes are “hidden” when DNA is in its native configuration, antibodies directed against ssDNA do not usually crossreact with dsDNA. Antibodies to ssDNA have the following general properties:
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- ANTI-DNA ANTIBODIES
- Anti-ssDNA antibodies
- Anti-dsDNA antibodies
- - Measurement of anti-dsDNA
- - Titer, pathogenicity, and disease activity
- ANTI-Sm AND ANTI-U1 RNP ANTIBODIES
- Anti-Sm antibodies
- Anti-U1 RNP antibodies
- Methods of measurement
- Clinical utility
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS