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Abstract Number: 793

Clinical Associations of Anti-U11/U12 (RNPC-3) Autoantibodies in Patients with Systemic Sclerosis

Lorenzo Beretta1, Michael Mahler2, Chelsea Bentow2, Andrea Seaman2, Fabrece Roup2, Michelle Amio2, Karl Norvell2, Jay Milo2, Susan Encabo2, Janire Perurena3, Maite Sanz3, Alfredo Guillen4, Ana Marín3, Vicent Fonollosa3, Eduardo Callejas3 and Carmen Pilar Simeón4, 1Scleroderma Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy, 2Research and Development, Inova Diagnostics, San Diego, CA, 3Scleroderma Unit, Internal Medicine Department, Vall d’Hebron Hospital, Barcelona, Spain, 4Scleroderma Unit, Internal Medicine Department, Vall d’Hebron Hospital, Barcelona, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: autoantibodies, diagnosis, prognostic factors and systemic sclerosis

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Session Information

Date: Sunday, October 21, 2018

Title: Systemic Sclerosis and Related Disorders – Clinical Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Anti-nuclear antibodies (ANA) are present in approximately 90% of sera from systemic sclerosis (SSc) patients and play an important role in the diagnosis and prognosis of SSc. Besides the classical autoantibodies that are part of the classification criteria (anti-Scl-70, anti-centromere, anti-RNA Pol III), several other antibodies can be found in SSc, albeit with lower prevalence, some of which clearly associate with disease phenotypes. Anti-U11/12 Ribonucleoprotein (RNP) antibodies have been reported in a small portion of patients with pulmonary fibrosis. RNPC-3, also known as U11/U12 Small Nuclear Ribonucleoprotein 65 KDa Protein has been reported as an autoantibody target with strong association with malignancy in patients with SSc. Here we aimed to study the prevalence of anti-RNPC-3 antibodies in SSc and controls.

Methods:

A total of 613 well characterized SSc patients from two different sites (Barcelona, n=225; and Milan, n=388) were used to establish sero-clinical associations. In addition, a variety of disease controls (rheumatoid arthritis, n=50; systemic lupus erythematosus, n=50; infectious disease, n=50; healthy individuals, n=50) were included to assess autoantibody specificity. All samples were tested on particles coated with recombinant RNPC-3 along with classical SSc markers (Scl-70, centromere, RNA Pol III) using a novel particle-based multi-analyte technology (PMAT, Inova Diagnostics, San Diego, USA). Disease subtype [limited (lcSSc) or diffuse SSc (dcSSc)] and clinical manifestations were retrieved from each site and included digital ulcers (39.2%), interstitial lung disease (ILD, 37.7%), scleroderma-related malignancy (16.7%), and calcinosis (22.7%).

Results:

In the total cohort, anti-RNPC-3 showed a prevalence of 3.1% (n=19) in SSc with 99.5% specificity, while the prevalence in each SSc cohort was 4.9% and 2.1% in the Spanish and Italian sites, respectively. Anti-RNPC-3 antibodies were found at very high titers in SSc versus controls (p<0.0001) and the majority of the positives (13/19, 68.4%) were negative for the classical SSc markers (anti-Scl-70, anti-centromere, anti-RNA Pol III). When analyzing against clinical manifestations in SSc, anti-RNPC-3 antibodies showed a strong association with ILD both in prevalence (Fisher Exact p=0.0062) and antibody levels (Wilcoxon-Mann-Whitney, p=0.0153), however the marker was not significantly associated with the other manifestations analyzed (cancer, ulcers, calcinosis). Although the marker showed higher prevalence in dcSSc (6.5% vs. 3.1% in lcSSc), the difference did not reach significance.

Conclusion:

Our study confirms the presence of anti-RNPC-3 autoantibodies in patients with SSc. In addition, this study of Spanish and Italian SSc patients confirms the association of anti-RNPC-3 with ILD as previously reported in a North American cohort. In contrast, we were unable to confirm the associations with cancer. Further studies are needed to verify the clinical utility of the marker and to further investigate the putative association with cancer.


Disclosure: L. Beretta, None; M. Mahler, Inova Diagnostics, 3; C. Bentow, Inova Diagnostics, 3; A. Seaman, Inova Diagnostics, 3; F. Roup, Inova Diagnostics, 3; M. Amio, Inova Diagnostics, 3; K. Norvell, Inova Diagnostics, 3; J. Milo, Inova Diagnostics, 3; S. Encabo, Inova Diagnostics, 3; J. Perurena, None; M. Sanz, None; A. Guillen, None; A. Marín, None; V. Fonollosa, None; E. Callejas, None; C. P. Simeón, None.

To cite this abstract in AMA style:

Beretta L, Mahler M, Bentow C, Seaman A, Roup F, Amio M, Norvell K, Milo J, Encabo S, Perurena J, Sanz M, Guillen A, Marín A, Fonollosa V, Callejas E, Simeón CP. Clinical Associations of Anti-U11/U12 (RNPC-3) Autoantibodies in Patients with Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/clinical-associations-of-anti-u11-u12-rnpc-3-autoantibodies-in-patients-with-systemic-sclerosis/. Accessed .
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