Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies

Arthritis Rheum. 2010 Sep;62(9):2787-95. doi: 10.1002/art.27549.


Objective: This study was undertaken to examine the temporal relationship between scleroderma development and malignancy, and to evaluate whether this differs by autoantibody status among affected patients.

Methods: Study participants had a diagnosis of scleroderma, a diagnosis of cancer, cancer, an available serum sample, and a cancer pathology specimen. Sera were tested for autoantibodies against topoisomerase I, centromere, and RNA polymerase I/III by immunoprecipitation and/or enzyme-linked immunosorbent assay. Clinical and demographic characteristics were compared across autoantibody categories. Expression of RNA polymerases I and III was evaluated by immunohistochemistry using cancerous tissue from patients with anti-RNA polymerase antibodies.

Results: Twenty-three patients were enrolled. Six patients tested positive for anti-RNA polymerase I/III, 5 for anti-topoisomerase I, and 8 for anticentromere, and 4 were not positive for any of these antigens. The median duration of scleroderma at cancer diagnosis differed significantly between groups (-1.2 years in the anti-RNA polymerase I/III group, +13.4 years in the anti-topoisomerase I group, +11.1 years in the anticentromere group, and +2.3 years in the group that was negative for all antigens tested) (P = 0.027). RNA polymerase III demonstrated a robust nucleolar staining pattern in 4 of 5 available tumors from patients with antibodies to RNA polymerase I/III. In contrast, nucleolar RNA polymerase III staining was not detected in any of 4 examined tumors from the RNA polymerase antibody-negative group (P = 0.048).

Conclusion: Our findings indicate that there is a close temporal relationship between the onset of cancer and scleroderma in patients with antibodies to RNA polymerase I/III, which is distinct from scleroderma patients with other autoantibody specificities. In this study, autoantibody response and tumor antigen expression are associated. We propose that malignancy may initiate the scleroderma-specific immune response and drive disease in a subset of scleroderma patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Antibodies, Antinuclear / blood*
  • Antibodies, Antinuclear / immunology
  • Centromere / immunology
  • Comorbidity
  • DNA Topoisomerases, Type I / immunology
  • Female
  • Humans
  • Male
  • Maryland / epidemiology
  • Middle Aged
  • Neoplasms / epidemiology*
  • RNA Polymerase I / immunology*
  • RNA Polymerase III / immunology*
  • Scleroderma, Systemic / enzymology
  • Scleroderma, Systemic / epidemiology*
  • Scleroderma, Systemic / immunology
  • Time Factors


  • Antibodies, Antinuclear
  • anti-extractable nuclear antigen antibodies
  • RNA Polymerase I
  • RNA Polymerase III
  • DNA Topoisomerases, Type I