Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis
| العنوان: | Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis |
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| المؤلفون: | Shaun M. Flint, Corrado Campochiaro, Emma Derrett-Smith, Jennifer Singh, Christopher P. Denton, Nicholas Galwey, Adam Taylor, Katherine Nevin, Kristina Clark, Voon H Ong, Eszter Csomor, Nicolas Wisniacki, Yee Voan Teo, Mary A. Morse |
| المصدر: | Annals of the Rheumatic Diseases. 80:1584-1593 |
| بيانات النشر: | BMJ, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Proteomics, 0301 basic medicine, Disease, Pathogenesis, 0302 clinical medicine, Fibrosis, Gene expression, Immunology and Allergy, Medicine, Prospective Studies, Hyaluronic Acid, skin and connective tissue diseases, Aged, 80 and over, integumentary system, biology, Middle Aged, DNA Topoisomerases, Type I, Antibodies, Antinuclear, Cohort, Disease Progression, Female, Antibody, Immunosuppressive Agents, Procollagen, Adult, Immunology, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, Rheumatology, Humans, Aged, Autoantibodies, 030203 arthritis & rheumatology, Tissue Inhibitor of Metalloproteinase-1, business.industry, Gene Expression Profiling, Autoantibody, RNA Polymerase III, medicine.disease, Peptide Fragments, Clinical trial, 030104 developmental biology, Case-Control Studies, Scleroderma, Diffuse, biology.protein, Transcriptome, business |
| الوصف: | ObjectivesClinical heterogeneity is a cardinal feature of systemic sclerosis (SSc). Hallmark SSc autoantibodies are central to diagnosis and associate with distinct patterns of skin-based and organ-based complications. Understanding molecular differences between patients will benefit clinical practice and research and give insight into pathogenesis of the disease. We aimed to improve understanding of the molecular differences between key diffuse cutaneous SSc subgroups as defined by their SSc-specific autoantibodiesMethodsWe have used high-dimensional transcriptional and proteomic analysis of blood and the skin in a well-characterised cohort of SSc (n=52) and healthy controls (n=16) to understand the molecular basis of clinical diversity in SSc and explore differences between the hallmark antinuclear autoantibody (ANA) reactivities.ResultsOur data define a molecular spectrum of SSc based on skin gene expression and serum protein analysis, reflecting recognised clinical subgroups. Moreover, we show that antitopoisomerase-1 antibodies and anti-RNA polymerase III antibodies specificities associate with remarkably different longitudinal change in serum protein markers of fibrosis and divergent gene expression profiles. Overlapping and distinct disease processes are defined using individual patient pathway analysis.ConclusionsOur findings provide insight into clinical diversity and imply pathogenetic differences between ANA-based subgroups. This supports stratification of SSc cases by ANA antibody subtype in clinical trials and may explain different outcomes across ANA subgroups in trials targeting specific pathogenic mechanisms. |
| تدمد: | 1468-2060 0003-4967 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0bfe0b2d30a93d414834be98b5dfacac https://doi.org/10.1136/annrheumdis-2021-220402 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0bfe0b2d30a93d414834be98b5dfacac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14682060 00034967 |
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