Background/Purpose: Systemic Sclerosis (SSc) patients with anti-RNA polymerase III (RNAP) antibody have been reported to have an increased risk of malignancy as compared with those with other disease-specific autoantibodies in Caucasian populations. The aim of this study was to investigate the relationship between disease-specific autoantibodies and malignancy, to examine the expression of RNAP in tumor tissues and to examine of the clinical features of cases with and without malignancy.

Methods: The study involved 208 Japanese patients with SSc consisting of 47 male and 161 female patients with a mean age of 63.1 ± 14.0 years. Of 208 patients, 52patients had diffuse cutaneous systemic sclerosis (dcSSc) and 156 had limited cutaneous systemic sclerosis (lcSSc). Fourteen patients (6.7%)had anti-RNAP antibody, 36 (17.3%) patients had anti-topoisomerase I (Topo I) antibody and 112 patients (53.8%) had anticentromere antibody (ACA), 19 patients had the other antibodies, and 27 patients had unknown antibodies. Malignant tumor tissues were stained using an anti-POLR3A antibody (Atlas antibodies, Sweden), which provided instructions for making the subunit A of RNA polymerase III.Statistical analysis: Statistical analysis was performed using the Mann-Whitney U test for determining the level of significance of differences between sample means. A p value less than 0.05 was considered statistically significant.

Results: The prevalence of malignancy was significantly higher in patients with RNAP antibody (8/14, 57.1%) than in those with Topo I antibody (2/36, 5.5%) and in those with ACA (5/112, 4.4%). Importantly, among 8 patients with RNAP antibody and malignancy, 5 patients (62.5%) developed malignancy from 2 years before to 1 years after SSc onset. Tumor tissues obtained from SSc patients with RNAP antibody complicated with malignancy were stained using POLR3A antibody. Expression of POLR3A protein was observed in the tumor tissue.Regarding other clinical correlation, RNAP poisitive SSc patients with malignancy exhibited increased male/all ratio relative to those without malignancy (75% vs 33% p< 0.05). The mean age of RNAP SSc patients with maligncay was significantly higher than without malignancy (66.9 vs 52.8 years old p< 0.05). RNAP SSc patients with malignancy had average modified Rodnan skin score (MRSS) less than those without malignancy (7.38 vs 21.5 p< 0.05).

Conclusion: Japanese SSc patients with RNAP have an increased risk of malignancy as compared with those with other disease-specific autoantibodies. This result was similar to previous reports in Caucasian populations. In SSc patients with RNAP antibody complicated with malignancy, it was shown that POLR3A protein was expressed frequently in tumor tissues. SSc patients with RNAP could be considered to share the same pathological process among different ethnic groups. Furthermore, among SSc patients with anti-RNAP antibody, it was considered that male, relatively old, and patients with low MRSS should pay attention especially to the complication of malignancy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-clinical-features-of-anti-rna-polymerase-iii-antibodypositive-systemic-sclerosis-with-and-without-malignancy/