Test performance in systemic sclerosis: anti-centromere and anti-Scl-70 antibodies

Am J Med. 1997 Sep;103(3):242-8. doi: 10.1016/s0002-9343(97)00023-5.

Abstract

Purpose: To determine the sensitivity and specificity of anti-centromere (ACA) and anti-Scl-70 antibodies in systemic sclerosis (SSc).

Methods: Four-hundred ninety-seven English language articles published from 1966 to 1994 were identified by structured MEDLINE search. Articles in which either ACA or anti-Scl-70 antibodies were measured in both SSc patients and a non-SSc control group were reviewed and rated using a previously published diagnostic testing scale. Reported sensitivity and specificity from each study was converted into a 2 x 2 table, and combined across studies to calculate summary rates for each antibody. Author's clinical classification criteria for SSc served as the gold standard for disease diagnosis.

Results: In 30 articles that fulfilled inclusion criteria, ACA were found in 441 of 1,379 SSc patients (sensitivity 32%, range 17% to 56%). This increased to 57% (332 of 585) in patients with the limited cutaneous, or CREST, subset of SSc (IcSSc). Anti-Scl-70 antibodies were found in 366 of 1,074 SSc patients (sensitivity 34%, range 3% to 75%), and this increased slightly to 40% in patients with the diffuse cutaneous form of SSc (dcSSc). Both antibodies were measured in 670 patients, and either test was positive in 58% (range 29% to 86%), but in only 3 patients were both antibodies present. The specificity of each antibody was high, but varied by control group. ACA were present in 5% and anti-Scl-70 antibodies were present in 2% of patients with other connective tissue diseases, but fewer than 1% of disease free controls had either antibody present.

Conclusions: As individual diagnostic tests in SSc, both ACA and anti-Scl-70 antibodies are highly specific. Each performs somewhat better as discriminators of clinical subsets for patients in whom a diagnosis of SSc has already been established. Clinicians can rely on a positive test result as being specific in the detection of disease, but 40% of SSc patients are likely to have neither antibody present, and a negative result does not exclude the diagnosis. Measurement of these antibodies should be considered secondary to the clinical features when making a diagnosis of SSc.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antibodies, Antinuclear / blood*
  • Autoantibodies / blood*
  • Centromere / immunology*
  • Diagnosis, Differential
  • Humans
  • Scleroderma, Systemic / diagnosis*
  • Scleroderma, Systemic / immunology*
  • Sensitivity and Specificity

Substances

  • Antibodies, Antinuclear
  • Autoantibodies