Background/Purpose: Anti-RNA polymerase III antibodies (anti-RNAP III) are one of the most frequent antinuclear antibodies identified in systemic sclerosis (SSc), with an estimated prevalence of 11% (95% CI: 8-14) (1). Anti-RNAP III has been associated with some clinical characteristics linked with a poor prognosis such as diffuse cutaneous involvement or renal crisis. More recently, anti-RNAP III have been suggested to play a role in immunological response to cancer (2). This study aimed to (i) confirm this clinical phenotype in a new French cohort followed by a systematic review and meta-analysis of the literature; (ii) test whether unknown clinical associations could be highlighted by a meta-analysis.

Methods: One hundred and thirty tree consecutive and unselected SSc patients were tested for anti-RNAP III. Clinical characteristics were retrieved from our database. PubMed and EMBase were searched for all references providing clinical characteristics of anti-RNAP III positive and negative (controls) SSc patients. Meta-analysis was performed using number of anti-RNAP III positive and controls patients, clinical characteristics and organ involvement.

Results: Twelve patients were found to be anti-RNAP III positive in our cohort. Anti-RNAP III was associated with diffuse cutaneous involvement (p=0.02), myositis, renal crisis and cancer (p=0.01). The systematic review retrieved 112 abstracts from 2003 references, which were read in full-text. Forty-five studies were finally included in the meta-analysis. The number of studies providing data for each clinical association was comprised between 4 and 26; between 256 to 1098 anti-RNAP III positive patients and 2088 to 6612 controls were included in analysis. Anti-RNAP III were positively associated with diffuse cutaneous involvement, joint involvement, renal crisis, heart involvement and cancer; and negatively associated with female sex. There was no association between anti-RNAP III and esophageal involvement, pulmonary hypertension, interstitial lung disease, digital ulceration, and myositis (Table 1).

Conclusion: This meta-analysis confirmed that SSc patients with anti-RNAP III are at higher risk of severe skin extension, renal crisis and cancer. Merging results from numerous studies also highlighted less known association such as joint and heart involvement. Patients carrying anti-RNAP III should benefit from an appropriate screening of these potentially severe complications.

(1) Sobanski V et al. Prevalence of Anti–RNA Polymerase III Antibodies in Systemic Sclerosis: New Data From a French Cohort and a Systematic Review and Meta-Analysis. Arthritis & Rheumatology 2014;66:407–417.

(2) Joseph CG et al. Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science 2014;343:152–157.

Table 1. Results of the meta-analysis

Clinical association	No. of studies	Anti-RNAP III positive patients*	Anti-RNAP III negative patients*	Odds ratio (95% CI)
Female sex	18	506/633	3939/4654	0.46 (0.22-0.96)
Diffuse cutaneous SSc	26	666/956	2037/6612	4.12 (2.72-6.24)
Pulmonary hypertension	16	63/684	557/4769	0.94 (0.68-1.29)
Interstitial lung disease	20	232/714	1842/5056	0.77 (0.56-1.07)
Digital ulceration	11	144/352	1277/3138	0.90 (0.61-1.33)
Joint involvement	12	266/411	1446/3382	1.94 (1.20-3.14)
Myositis	10	65/453	625/3178	1.58 (0.92-2.73)
Esophageal involvement	10	196/256	1427/2088	0.90 (0.61-1.32)
Renal crisis	22	251/1098	256/6234	8.86 (6.48-12.13)
Heart involvement	16	113/583	509/3721	1.79 (1.10-2.91)
Cancer	4	59/361	165/2608	4.12 (2.26-7.51)

* number of events/number of patients

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