PO:31:174 | Increased frequency of anti-RNA polymerase 3 antibodies in patients with systemic sclerosis and silicone breast implants: a multicentre study from the international European Scleroderma Trials and Research cohort

Maria Grazia Lazzaroni¹, Yolanda Braun-Moscovici², Elda Piovani¹, Claudia Barison¹, Liala Moschetti¹, Veronica Batani³, Corrado Campochiaro³, Michal Tomcik⁴, Francesca Motta⁵, Maria De Santis⁵, Petros P. Sfikaki⁶, Masataka Kuwana⁷, Brigitte Granel⁸, Roberta Foti⁹, Virginia Berlingiero¹⁰, Joana Caetano¹¹, Yannick Allanore¹², Alexandra Balbir-Gurman², Marco Matucci Cerinic³, Franco Franceschini¹, Paolo Airò¹. | ¹ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy; ²Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Israeli Institute of Tecnology, Haifa, Israel; ³Vita-Salute San Raffaele University, San Raffaele Hospital, Milano, Italy; ⁴Institute of Rheumatology, Praga, Czech Republic; ⁵IRCCS Humanitas Research Hospital; Humanitas University, Milano, Italy; ⁶Joint Rheumatology Program, Medical School, National Kapodistrian University of Athens Atene GREECE; ⁷Nippon Medical School Hospital Tokyo Japan; ⁸Hôpital Nord de Marseille; Aix-Marseille Université Marsiglia France; ⁹AOU Policlinico G. Rodolico San Marco, Catania, Italy; ¹⁰Azienda Ospedaliera Universitaria Senese, Siena, Italy; ¹¹Fernando Fonseca Hospital, Amadora, Portugal; ¹²Université Paris Cité, Cochin Hospital, Parigi, France.

Background. Systemic Sclerosis (SSc) is a heterogeneous systemic autoimmune disease, in which distinct disease subsets can be identified with autoantibodies. In a large EUSTAR study including >4,000 SSc patients, anti-RNA polymerase III (anti-RNAP3) was positive in 4.5% and their clinical phenotype included malignancies synchronous to disease onset and specifically breast cancer. Noteworthy, one study from Italy and one from Japan reported a specific association of silicone breast implants (SBI) with anti-RNAP3 positivity in SSc females, raising the possibility of a new clinical association of this autoantibody. The study aims to analyse the characteristics of female SSc patients with SBI implanted before the disease onset, and to compare them with female SSc patients without SBI.

Materials and Methods. International case-control study within the EUSTAR network (CP-117), including SSc females with SBI implanted before SSc onset (cases) and 2-3 SSc female patients without SBI (controls) matched for cutaneous subset, age at onset (±5 years) and disease duration (±2 years). Data regarding indication for SBI implantation and rupture (cases) and on breast cancer (cases and controls) were recorded.

Results. 41 SSc patients with SBI (cases) and 119 matched controls were collected from 12 centres. Among 41 cases, the majority had SBI implanted for cosmetic reasons (82.9%) and had diffuse cutaneous involvement (dcSSc,58.5%), with anti-RNAP3 positivity in 31.7%. Anti-RNAP3+ patients, as compared to anti-RNAP3- had a tendency toward higher frequency of documented SBI rupture (p:0.089). As compared to 119 matched controls, patients with SBI had higher frequency of anti-RNAP3 positivity (31.7% vs 14.3%, p:0.020, [OR 2.78, 95% CI 1.20-6.42]). No difference in the rate of breast cancer was observed, with no cases of breast cancer synchronous in both groups. Clinical characteristics were similar in cases and controls, except for lower prevalence of clinically relevant arrythmias and higher prevalence of ever smoker in SBI patients (Table1). Interstitial lung disease (ILD) was slightly less frequent in SBI+ (46.3% vs 60.0%,p:0.144) with NSIP being the most frequent pattern in both groups. A tendency toward a better functional outcome in terms of pFVC% at last visit was observed for SBI+ ILD patients (p:0.087).

Conclusions. In this multicentre international cohort, patients with SSc and SBI implanted before disease onset showed dcSSc in more than half of cases and had a higher rate of anti-RNAP3 positivity as compared to the expected frequency and to matched controls. SBI were mainly implanted for cosmetic reasons and no cases of synchronous breast cancer were detected in both groups, highlighting that the association with anti-RNAP3 with SBI is independent from the one with breast cancer previously documented. Clinical features were similar to those of matched controls, except for lower prevalence of arrhythmias in cases. Further enrichment of the cohort will allow subgroup analysis of SBI patients.