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Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis

M Kuwana1, J Kaburaki, T Mimori

  • 1Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

The Journal of Clinical Investigation
|April 1, 1993
PubMed

Insights

Researchers found a new autoantibody targeting all three RNA polymerases in systemic sclerosis (SSc) patients. This anti-RNA polymerase antibody is specific to SSc, particularly diffuse cutaneous SSc, and indicates a poor prognosis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis.
  • Nuclear autoantibodies are common in SSc, but novel targets are continually being identified.
  • RNA polymerases are essential enzymes for gene transcription.

Purpose of the Study:

  • To identify novel autoantibodies in patients with systemic sclerosis (SSc).
  • To characterize the reactivity and clinical significance of an autoantibody targeting RNA polymerases in SSc.

Main Methods:

  • Sera from SSc patients were used for immunoprecipitation assays with labeled cell extracts.
  • Inhibition assays were performed to assess the effect of purified IgG on RNA transcription.
  • Immunoblot analysis was conducted using RNA polymerase-enriched fractions.

Main Results:

  • A novel autoantibody reactive with all three classes of RNA polymerases (I, II, and III) was identified in 14 out of 275 SSc sera.
  • The autoantibody inhibited RNA transcription in vitro.
  • Anti-RNA polymerase antibody was highly specific for SSc, particularly diffuse cutaneous SSc, and associated with heart/kidney involvement and poor survival.

Conclusions:

  • A novel autoantibody targeting RNA polymerases is identified in a subset of SSc patients.
  • This autoantibody serves as a potential biomarker for a unique subset of diffuse cutaneous SSc.
  • The presence of this antibody is linked to significant organ involvement and reduced survival rates.

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