Serology of Systemic Lupus Erythematosus
A 13 year old girl with a photosensitive malar rash, painless oral ulcers, polyarthritis of the hands and knees, and 2+ proteinuria is being evaluated for systemic lupus erythematosus. Hemoglobin is 98 g/L, white cell count 2.9 × 10⁹/L, and serum creatinine 62 µmol/L. Her antinuclear antibody is positive at 1:1280 in a homogeneous pattern and C3 is low. Which antibody is the most specific for systemic lupus erythematosus?
- A.Anti Smith antibodyCorrect
- B.Antinuclear antibody
- C.Anti double stranded DNA antibody
- D.Anti histone antibody
Explanation
Anti Smith antibody, directed against small nuclear ribonucleoproteins, is the most specific serological marker for systemic lupus erythematosus, with a specificity approaching 98 to 99 percent, so a positive result essentially secures the diagnosis. Its major limitation is low sensitivity, since only about 20 to 30 percent of patients with lupus are anti Smith positive, and unlike anti double stranded DNA its titre does not track disease activity. Antinuclear antibody is the most sensitive test, positive in more than 95 percent of patients with lupus, which makes it the ideal screening test, but it lacks specificity because it is also found in juvenile idiopathic arthritis, other connective tissue diseases, thyroid disease, chronic infections and up to 15 percent of healthy children, so a positive antinuclear antibody alone never diagnoses lupus. Anti double stranded DNA is also highly specific at about 95 to 96 percent, slightly below anti Smith, but it is far more useful clinically because its titre correlates with disease activity, particularly nephritis, and it is used serially alongside C3 and C4 to monitor therapy. Anti histone antibody is characteristic of drug induced lupus caused by agents such as hydralazine, procainamide, isoniazid and minocycline, a syndrome that spares the kidneys and central nervous system and resolves on stopping the drug. Other lupus associated antibodies include anti Ro and anti La, which are linked to neonatal lupus and congenital heart block, and antiphospholipid antibodies, which predict thrombosis. In practice both anti Smith and anti double stranded DNA are ordered when the antinuclear antibody screen is positive.
Why each option
- A.
- Correct. Anti Smith antibody has the highest specificity for systemic lupus erythematosus at about 98 to 99 percent, although its sensitivity is only 20 to 30 percent.
- B.
- Antinuclear antibody is the most sensitive screening test but is far too non specific, occurring in many other conditions and in healthy children.
- C.
- Anti double stranded DNA is highly specific at about 95 to 96 percent, marginally less than anti Smith, but it is the preferred marker for monitoring activity.
- D.
- Anti histone antibody characterises drug induced lupus rather than idiopathic systemic lupus erythematosus.
Reference: Nelson Textbook of Pediatrics, 22nd ed., 2024, Systemic Lupus Erythematosus
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