Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis
| Autor: | 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 |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Contracture Chromosomal Proteins Non-Histone Immunoblotting Autoantigens Article Cohort Studies Sex Factors Neoplasms Humans Esophageal Motility Disorders Receptors Platelet-Derived Growth Factor Telangiectasis Ku Autoantigen Aged Autoantibodies Principal Component Analysis Scleroderma Systemic Exosome Multienzyme Ribonuclease Complex Smoking Australia RNA Polymerase III RNA-Binding Proteins Antigens Nuclear Raynaud Disease Middle Aged DNA-Binding Proteins DNA Topoisomerases Type I Ribonucleoproteins Exoribonucleases Female Centromere Protein B Gastric Antral Vascular Ectasia Pol1 Transcription Initiation Complex Proteins Centromere Protein A |
| Zdroj: | Arthritisrheumatology (Hoboken, N.J.). 67(12) |
| ISSN: | 2326-5205 |
| Popis: | To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort.Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data.A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures.Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease. |
| Databáze: | OpenAIRE |
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