Interpretation of an Extended Autoantibody Profile in a Well‐Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis

K A Patterson, P J Roberts-Thomson, S Lester, J A Tan, P Hakendorf, M Rischmueller, J Zochling, J Sahhar, P Nash, J Roddy, C Hill, M Nikpour, W Stevens, S M Proudman, J G Walker

To determine the relationships between systemic sclerosis (SSc) related autoantibodies (AA), and their clinical associations, in a well characterised Australian patient cohort. Serum from 505 Australian SSc patients were analysed with a line immunoassay (EUROLINE, Euroimmun, Lubeck, Germany) for AA to centromere (CENP) A and B, RNA polymerase III (RNAP3) (11 and 155 epitopes), NOR-90, Fibrillarin, Th/To, PMScl-75 and PMScl-100, Ku, Topoisomerase-1 (Topo1), TRIM21/Ro52 and PDGF-Receptor (PDGFR). Patient subgroups were identified by hierarchical clustering of the first two dimensions of a Principal Components Analysis (PCA) of quantitative AA scores. Results were compared with detailed clinical data. 449/505 patients were positive for at least one immunoblot AA. Heatmap visualisation of AA scores, and PCA clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP3 and Topo1. Five patient clusters were identified (CENP, RNAP3 'strong', RNAP3 'weak', Topo1, "Other"). Clinical features associated with CENP, RNAP3 and Topo1 were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP3 into two clusters. RNAP3 'strong' patients had an increased risk of gastric antral vascular ectasia, but a lower risk of oesophageal dysmotility. "Other" patients were more likely to be males and have a history of smoking and malignancy, but less likely to have telangiectasia, Raynaud's phenomenon and joint contractures. Five major autoantibody clusters, with specific clinical and serological associations, were identified in Australian SSc patients. Sub-classification and disease stratification utilising AAs, may have clinical utility, particularly in early disease. This article is protected by copyright. All rights reserved.