All of the following are characteristic autoantibodies in systemic lupus erythematosus (SLE) EXCEPT:

Question

Accepted Answer

A. Anti-centromere antibodies (ACA) as the most common autoantibody in SLE. ## 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.

Answer

B. Anti-histone antibodies associated with drug-induced lupus

Answer

C. Anti-Smith (anti-Sm) antibodies directed against snRNP core proteins

Answer

D. Anti-double-stranded DNA (anti-dsDNA) antibodies with high specificity for SLE

All of the following are characteristic autoantibodies in systemic lupus erythematosus (SLE) EXCEPT:

Explanation

Autoantibodies in SLE: Specificity and Prevalence

SLE-Specific and Associated Autoantibodies

Why Each Correct Option Belongs in SLE

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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