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Autoantibody Formation Precedes Development of Systemic Lupus Erythematosus

Autoantibodies develop over time, and their presence in asymptomatic patients may presage clinical disease.

Clinicians have long been aware that some patients with suspected systemic lupus erythematosus (SLE) have a long, gradual onset of disease. Only after months, or even years, do sufficient clinical and laboratory criteria become evident to confirm the diagnosis. What happens before the onset of clinical disease has not been fully elucidated. These authors had a unique opportunity to study the prediagnosis development of autoantibodies in the sera of 130 patients who developed SLE; the patients were identified from among more than 5 million U.S. armed forces personnel with stored sera.

The authors found that antinuclear antibodies, antiphospholipid antibodies, and anti-Ro and anti-La antibodies were present before more SLE-specific ones, such as anti-Sm, ant-RNP, and anti-nDNA antibodies. They found sequential development of autoantibodies in subjects with multiple samples. There was a marked difference in the prevalence of antibodies in the SLE group and in age-, sex-, and race-matched controls (88% vs. 3.8%). The authors conclude that autoantibodies are typically present for many years before diagnosis and that there is a predictable, progressive accumulation of specific antibodies during the asymptomatic period. They postulate that genetic and environmental factors have a role in disease development, which moves from normal immunity to benign autoimmunity, pathogenic autoimmunity, and eventual clinical disease.

Comment: The authors' observations are very important. We administer biologic agents, particularly tumor necrosis factor-alpha antagonists, for the control of inflammatory disease, but many patients develop autoantibodies without apparent clinical disease. It is unclear what should be done about autoantibodies in asymptomatic patients. Although reassurance is reasonable for such patients, these data suggest that reevaluation of clinical status is indicated.

— Jeffrey P. Callen, MD

Published in Journal Watch Dermatology November 12, 2003

Citation(s):

Arbuckle MR et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003 Oct 16; 349:1526-33.

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Shmerling RH. Autoantibodies in systemic lupus erythematosus -- there before you know it. N Engl J Med 2003 Oct 16; 349:1499-500.

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• Medline abstract (Free)