These investigators are studying why cancer is often detected around the time that scleroderma is diagnosed. Building on their previous work showing that cancer may trigger the autoimmune response in scleroderma, this team now provides data showing that while some autoantibodies are associated with increased cancer incidence (e.g., anti-RNA pol III antibodies), combinations of these antibodies with others (e.g., anti-RNA pol III + anti-RPA194) may protect against cancer.
Why was this study done?
Previously, these researchers found that 15% of scleroderma patients with autoantibodies against RNA pol III have a cancer diagnosed around the same time that scleroderma develops. Those cancers often have mutations in the POLR3A gene, which encodes the RNA pol III protein, suggesting that mutation of the gene initiates an immune response against the mutant protein. This immune response subsequently broadens to include normal versions of the protein and suggests a scenario in which cancer triggers the development of autoimmunity. In the current study, the authors investigated whether there was something unique about the 85% of patients with anti-RNA pol III antibodies who do not have a cancer diagnosis.
How was this study done?
The Johns Hopkins Scleroderma Center followed a group of 168 patients with anti-RNA pol III antibodies for five years and tracked the development of cancer in these patients. After this period, they compared the antibodies present in those patients with and without a detectable cancer.
What were the major findings?
The authors focused on people with scleroderma who had antibodies to RNA pol III and found a new antibody that was enriched in people who did not develop cancer. They found that 18.2% of the patients without cancer also made antibodies against the large subunit of RNA polymerase I (called anti-RPA194) – compared to only 3.8% of those with cancer.
What is the impact of the work?
These new data suggest that cancers present at levels too low to be detected clinically may still trigger an immune response against the tumor. In those patients who mount multiple different immune responses (e.g., antibodies against both RNA pol I and RNA pol III), there may be a greater chance that the cancer will be eliminated by the immune system. A byproduct of the immune response against cancer may be the development of scleroderma in some people. Clinically important questions raised by these studies include whether autoantibodies may be useful biomarkers to assess cancer risk for newly diagnosed scleroderma patients, whether “cancer-protective” antibodies may be used for cancer therapy, and whether treating an underlying cancer will also effectively treat scleroderma.
This research supported by:
- National Institutes of Health. Grant Numbers: 1R01 AR073208, K23 AR061439, P30‐AR070254, R01 GM12104
- Scleroderma Research Foundation
- Donald B. and Dorothy L. Stabler Foundation
Ami A. Shah, Antony Rosen, and Livia Casciola-Rosen (Rheumatology)
Marikki Laiho (Radiation Oncology)
Others in the Rheumatology Team: Adrianne Woods (data management and quality control), Margaret Sampedro (acquisition of biologic samples), and Drs. Laura Gutierrez-Alamillo and Qingyuan Yang (expert technical assistance).