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Abstract Number: 0395

RNA Polymerase III Autoantibody Levels and Risk of Systemic Sclerosis in Patients with Raynaud Phenomenon

Megan Lockwood1, Yuqing Zhang2, Marcy Bolster1, Sara Schoenfeld1, Xiaoqing Fu1, Seth Brownmiller1, Ana Fernandes1 and Flavia Castelino1, 1Massachusetts General Hospital, Boston, MA, 2Massachusetts General Hospital, Quincy, MA

Meeting: ACR Convergence 2021

Keywords: Biomarkers, Epidemiology, Raynaud's phenomenon, Scleroderma

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Session Information

Date: Saturday, November 6, 2021

Session Title: Systemic Sclerosis & Related Disorders – Clinical Poster I (0387–0413)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: Raynaud phenomenon is often the initial manifestation in systemic sclerosis (SSc) and can precede other SSc symptoms by years (1). Several SSc-specific autoantibodies are useful to identify patients with isolated Raynaud phenomenon (RP) at risk of progression to SSc (2). Anti-RNA polymerase III (anti-RNAP III) is associated with diffuse skin thickening, risk for renal crisis, and malignancy (3,4). The level of anti-RNAP III in patients with RP and the risk of progression to SSc has not previously been evaluated. We examined the relationship between anti-RNAP III levels and SSc risk among patients with RP.

Methods: We performed a retrospective cohort analysis of anti-RNAP III positive patients with RP seen at a US tertiary hospital system between January 1, 2010 and December 31, 2020. SSc diagnosis was determined through medical record review utilizing the 2013 ACR-EULAR classification criteria. Anti-RNAP III levels were classified into three categories: weak (20-39 units), moderate (40-80 units), and strong positive ( > 80 units). We estimated the rate of developing SSc for each anti-RNAP III category and examined their relation using a cause-specific Cox-proportional hazard model accounting for competing risk of death. In the multivariable regression model, we adjusted for socio-demographic and lifestyle factors, family history of rheumatic disease, comorbidities, and several laboratory results.

Results: We identified 118 patients with anti-RNAP III and RP. Patients with strong positive anti-RNAP III levels were more likely to be older, have negative centromere antibodies, a smoking history, a malignancy history, puffy hands, and skin thickening (Table 1). During 604 person-years of follow up, 79 patients developed SSc. The rate of SSc development was 9.3, 8.6, and 18.3 per 100-person-years among patients with weak, moderate, and strong positive anti-RNAP III levels, respectively (Table 2). Compared with those with weak anti-RNAP III levels, adjusted hazard ratios for patients with moderate and strong positive anti-RNAP III levels were 1.49 (95% CI: 0.74-3.01) and 2.88 (95% CI: 1.53-5.41), respectively (P for trend < 0.003).

Conclusion: Patients with high levels of anti-RNAP III had a much higher risk of progression to SSc than those with moderate and weak levels. Our findings suggest the level of anti-RNAP III is a strong predictor for the risk of SSc among patients with RP and those with high levels of anti-RNAP III should be closely monitored for development of SSc.

References

1. Maricq H, et al. Disease, Microvascular abnormalities as possible predictors of disease subsets in Raynaud phenomenon and early connective tissue. Clin Exp Rheumatol 1983;1:195–205.

2. Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 2005;35:35–42.

3. Nikpour M, et al. Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: A cross-sectional analysis of data from an Australian cohort. Arthritis Res Ther 2011;13.

4. Moinzadeh P, et al. Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Res Ther 2014;16.


Disclosures: M. Lockwood, None; Y. Zhang, None; M. Bolster, Johnson and Johnson, 11, Genentech, 5, Corbus, 5, Cumberland, 5, PracticeUpdate, 12, Associate Editor, Custom Learning Designs, 2; S. Schoenfeld, None; X. Fu, None; S. Brownmiller, None; A. Fernandes, None; F. Castelino, Boehringer Ingelheim, 2, Kadmon, 5.

To cite this abstract in AMA style:

Lockwood M, Zhang Y, Bolster M, Schoenfeld S, Fu X, Brownmiller S, Fernandes A, Castelino F. RNA Polymerase III Autoantibody Levels and Risk of Systemic Sclerosis in Patients with Raynaud Phenomenon [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/rna-polymerase-iii-autoantibody-levels-and-risk-of-systemic-sclerosis-in-patients-with-raynaud-phenomenon/. Accessed February 3, 2023.
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