What is the specificity of anti-dsDNA (double-stranded deoxyribonucleic acid) and anti-Sm (Smith) antibodies for Systemic Lupus Erythematosus (SLE)?

Specificity of Anti-dsDNA and Anti-Smith Antibodies for Systemic Lupus Erythematosus (SLE)

Anti-dsDNA antibodies have high specificity (97-99%) for SLE diagnosis, particularly when detected by the Crithidia luciliae immunofluorescence test (CLIFT) method, while anti-Smith (anti-Sm) antibodies are even more specific (95-100%) though less sensitive. 1, 2

Anti-dsDNA Antibodies

• Anti-dsDNA antibodies are heterogeneous and can target various DNA structures, including single-stranded DNA, left-handed dsDNA, right-handed dsDNA, and other nucleic acid structures 1, 2
• The specificity of anti-dsDNA for SLE varies by detection method:
  • CLIFT method: Highest specificity (nearly 100%) but lower sensitivity 1, 2
  • Solid-phase assays (SPA): Higher sensitivity but lower specificity 1
  • When both SPA and CLIFT are positive, SLE diagnosis is very likely 2
• False positives can occur in other autoimmune conditions, bacterial, viral, and parasitic infections, and cancer 1
• Anti-dsDNA antibodies are strongly associated with lupus nephritis and other SLE manifestations including skin involvement and certain neuropsychiatric disorders 1, 3

Anti-Smith (Anti-Sm) Antibodies

• Anti-Sm antibodies target spliceosome small nuclear ribonucleoproteins 1
• Extremely high specificity for SLE (95-100%), making them valuable diagnostic markers 2, 4
• Lower sensitivity than anti-dsDNA (approximately 25-30% at 99% specificity) 4
• Particularly valuable in anti-dsDNA-negative SLE patients (14.8% of anti-dsDNA-negative patients may be positive for anti-Sm) 4
• Associated with renal involvement, neurologic disorders, and constitutional symptoms 4

Clinical Application Algorithm

1. For suspected SLE with positive ANA:

   • Test for both anti-dsDNA and anti-Sm antibodies 1
   • If anti-dsDNA is positive by both SPA and CLIFT: SLE is very likely 1
   • If anti-dsDNA is positive by SPA only: SLE is likely but requires clinical correlation 1
   • If anti-dsDNA is negative but anti-Sm is positive: SLE is still likely (occurs in ~15% of cases) 4

2. For disease monitoring:

   • Anti-dsDNA antibodies show stronger correlation with disease activity than anti-Sm 5, 6
   • Use quantitative anti-dsDNA assays from the same laboratory for consistent monitoring 1
   • Anti-Sm monitoring may be helpful specifically in patients with active lupus nephritis 4

Important Clinical Considerations

• Neither antibody predicts long-term damage in SLE 7
• More than half (51.4%) of anti-dsDNA-positive patients are also positive for anti-Sm 4
• Changes in anti-Sm antibody titer over time correlate with alterations in disease activity 6
• A negative result for both antibodies does not rule out SLE, as some patients may be seronegative initially 2
• Anti-nucleosome antibodies may be useful when clinical suspicion for SLE is high but both anti-dsDNA and anti-Sm are negative 5

Pitfalls and Caveats

• Different laboratories may use different detection methods and cutoff values, affecting result interpretation 2
• Anti-dsDNA antibodies detected in clinical practice differ in their binding capacity to different assays 1
• Some patients may have persistently positive antibodies without clinical disease activity (serologically active, clinically quiescent) 1
• The conception of anti-dsDNA as a uniform group of antibodies is incorrect; they represent a heterogeneous set of antibodies with different specificities 1