## Autoantibodies in SLE: Specificity and Prevalence **Key Point:** Anti-centromere antibodies (ACA) are NOT characteristic of SLE; they are the hallmark of limited cutaneous systemic sclerosis (lcSSc) and primary biliary cholangitis (PBC), not SLE. ### SLE-Specific and Associated Autoantibodies | Autoantibody | Specificity for SLE | Frequency in SLE | Clinical Association | |---|---|---|---| | Anti-dsDNA | Very high (95–98%) | 60–70% | Lupus nephritis, disease activity | | Anti-Smith (Sm) | Virtually 100% | 20–30% | Highly specific, rare in other diseases | | Anti-histone | Low (not specific) | 50–60% | Drug-induced lupus (procainamide, hydralazine) | | Anti-centromere (ACA) | Very low in SLE | <5% | Limited scleroderma, PBC (80–90%) | | Anti-Ro/SSA | Moderate | 40–60% | Neonatal lupus, photosensitivity | | Anti-La/SSB | Moderate | 30–50% | Sjögren syndrome overlap | **High-Yield:** Anti-centromere antibodies are a **negative predictor** for SLE and point toward **scleroderma spectrum** or **PBC** instead. ### Why Each Correct Option Belongs in SLE 1. **Anti-dsDNA**: Gold standard for SLE diagnosis; correlates with lupus nephritis and disease activity [cite:Robbins 10e Ch 6]. 2. **Anti-Smith**: Pathognomonic for SLE; found in ~25% of patients but virtually never in other autoimmune diseases. 3. **Anti-histone**: Common in both SLE (50–60%) and drug-induced lupus; not SLE-specific but associated with the disease. **Clinical Pearl:** A patient with positive ACA but negative anti-dsDNA and anti-Sm should raise suspicion for **scleroderma or PBC**, not SLE.
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