High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum

Anti-Ro/SS-A antibodies are prevalent across systemic autoimmune rheumatic diseases (SARDs) and may signify a distinctive phenotype. This study aimed to identify protein biomarkers associated with symptom burden and health-related quality of life (HR-QoL), and use protein-based stratification to ide...

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Main Authors: Sarah Dyball, Rudresh Shukla, Anastasia-Vasiliki Madenidou, Maya H. Buch, Ian N. Bruce, Ben Parker
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Autoimmunity
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Online Access:https://www.tandfonline.com/doi/10.1080/08916934.2024.2433237
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author Sarah Dyball
Rudresh Shukla
Anastasia-Vasiliki Madenidou
Maya H. Buch
Ian N. Bruce
Ben Parker
author_facet Sarah Dyball
Rudresh Shukla
Anastasia-Vasiliki Madenidou
Maya H. Buch
Ian N. Bruce
Ben Parker
author_sort Sarah Dyball
collection DOAJ
description Anti-Ro/SS-A antibodies are prevalent across systemic autoimmune rheumatic diseases (SARDs) and may signify a distinctive phenotype. This study aimed to identify protein biomarkers associated with symptom burden and health-related quality of life (HR-QoL), and use protein-based stratification to identify clinically meaningful clusters and inflammatory pathways implicated. Anti-Ro positive SARD patients were enrolled in a 6-month pilot study. HR-QoL was determined using a patient-reported visual analogue scale, and symptom burden was assessed with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI). Proximity extension immunoassays measured normalized protein expression (NPX) across 92 inflammatory proteins. Linear regression identified proteins linked to patient outcomes. Unsupervised hierarchical clustering of baseline NPX identified patient clusters. Functional protein association networks were visualized using String V.12.0. Diagnostic groups showed no differences in HR-QoL or physician global assessment (PhGA). Poor HR-QoL and high symptom burden correlated with downregulated inflammatory proteins, while PhGA correlated with upregulated proteins. Two distinct clusters were identified; Cluster 1, ‘low expression cluster’ exhibited higher symptom burden and more impaired HR-QoL, while Cluster 2, ‘high expression cluster’ correlated with a higher physician global assessment (PhGA). Key hub proteins included TGF-β1, CXCL-8, and CCL-2. This study identified patient clusters across the Ro-positive SARD, linking symptom burden to specific proteomic profiles. Unraveling novel protein networks associated with symptom burden and poor HR-QoL may identify therapeutic targets, which address patient-reported outcome measures (PROMs) across several disease indications.
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spelling doaj-art-217d0d79d9dc40dd8d4c1daa925370db2025-08-20T02:30:34ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2024-12-0157110.1080/08916934.2024.2433237High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrumSarah Dyball0Rudresh Shukla1Anastasia-Vasiliki Madenidou2Maya H. Buch3Ian N. Bruce4Ben Parker5Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UKCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UKCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UKCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UKCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UKThe Kellgren Centre for Rheumatology, Manchester University Hospitals NHS Foundation Trust, Manchester, UKAnti-Ro/SS-A antibodies are prevalent across systemic autoimmune rheumatic diseases (SARDs) and may signify a distinctive phenotype. This study aimed to identify protein biomarkers associated with symptom burden and health-related quality of life (HR-QoL), and use protein-based stratification to identify clinically meaningful clusters and inflammatory pathways implicated. Anti-Ro positive SARD patients were enrolled in a 6-month pilot study. HR-QoL was determined using a patient-reported visual analogue scale, and symptom burden was assessed with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI). Proximity extension immunoassays measured normalized protein expression (NPX) across 92 inflammatory proteins. Linear regression identified proteins linked to patient outcomes. Unsupervised hierarchical clustering of baseline NPX identified patient clusters. Functional protein association networks were visualized using String V.12.0. Diagnostic groups showed no differences in HR-QoL or physician global assessment (PhGA). Poor HR-QoL and high symptom burden correlated with downregulated inflammatory proteins, while PhGA correlated with upregulated proteins. Two distinct clusters were identified; Cluster 1, ‘low expression cluster’ exhibited higher symptom burden and more impaired HR-QoL, while Cluster 2, ‘high expression cluster’ correlated with a higher physician global assessment (PhGA). Key hub proteins included TGF-β1, CXCL-8, and CCL-2. This study identified patient clusters across the Ro-positive SARD, linking symptom burden to specific proteomic profiles. Unraveling novel protein networks associated with symptom burden and poor HR-QoL may identify therapeutic targets, which address patient-reported outcome measures (PROMs) across several disease indications.https://www.tandfonline.com/doi/10.1080/08916934.2024.2433237Undifferentiated connective tissue diseasesystemic lupus erythematosusSjögren’s diseaseproteomicspatient-reported outcomes
spellingShingle Sarah Dyball
Rudresh Shukla
Anastasia-Vasiliki Madenidou
Maya H. Buch
Ian N. Bruce
Ben Parker
High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum
Autoimmunity
Undifferentiated connective tissue disease
systemic lupus erythematosus
Sjögren’s disease
proteomics
patient-reported outcomes
title High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum
title_full High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum
title_fullStr High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum
title_full_unstemmed High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum
title_short High throughput multiplex immunoassays stratify patients according to symptom burden across the anti-Ro positive systemic autoimmune rheumatic disease spectrum
title_sort high throughput multiplex immunoassays stratify patients according to symptom burden across the anti ro positive systemic autoimmune rheumatic disease spectrum
topic Undifferentiated connective tissue disease
systemic lupus erythematosus
Sjögren’s disease
proteomics
patient-reported outcomes
url https://www.tandfonline.com/doi/10.1080/08916934.2024.2433237
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