A 28-year-old woman presents with photosensitive malar rash, arthralgia, and persistent proteinuria (1.5 g/day). ANA is positive. Which investigation is most specific for confirming the diagnosis of SLE and assessing disease activity?

## Confirmatory Investigations in SLE **Key Point:** Anti-dsDNA (double-stranded DNA) antibodies are the most specific antibodies for SLE, present in 60–70% of patients. Low serum complement levels (C3, C4) indicate active disease and correlate with lupus nephritis. ### Diagnostic Criteria & Specificity | Investigation | Sensitivity in SLE | Specificity for SLE | Clinical Significance | |---|---|---|---| | ANA | 95–98% | Low (positive in many conditions) | Screening test; high NPV | | Anti-dsDNA | 60–70% | 95–98% | Confirmatory; correlates with nephritis | | Anti-Smith (Sm) | 20–30% | 99% | Highly specific but low sensitivity | | Low C3/C4 | 40–60% | Moderate | Marker of active disease | | Anti-histone | 70% | Low | Associated with drug-induced LE | **High-Yield:** Anti-dsDNA + low complement = active lupus nephritis. This combination is part of the ACR/EULAR SLE classification criteria and is essential for confirming diagnosis in a seropositive patient with clinical features. ### Why This Patient Needs Anti-dsDNA + Complement 1. **Proteinuria (1.5 g/day)** suggests lupus nephritis — anti-dsDNA and low complement are hallmarks of proliferative renal disease. 2. **ANA is positive but non-specific** — anti-dsDNA adds diagnostic specificity (>95%). 3. **Complement levels** assess disease activity and predict renal flares. **Clinical Pearl:** A patient with ANA+ and clinical SLE features but negative anti-dsDNA is still SLE (seronegative SLE exists), but anti-dsDNA presence strongly supports the diagnosis and indicates higher risk of nephritis. **Mnemonic: SLED** — Smith, dsDNA, and complement (C3/C4) are the three most specific SLE antibodies and markers. [cite:Harrison 21e Ch 297]