Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome: proteomic and network analysis.

Autor:	Berry JS; Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK., Tarn J; Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK., Casement J; Bioinformatics Support Unit, Newcastle University, Newcastle upon Tyne, UK., Duret PM; Department of Rheumatology, Civilian Hospitals Colmar, Colmar, France., Scott L; Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK., Wood K; Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK., Johnsen SJ; Department of Rheumatology, Stavanger University Hospital, Stavanger, Norway., Nordmark G; Medical Sciences, Uppsala University, Uppsala, Sweden., Devauchelle-Pensec V; Lymphocytes B et auto-immunité, Inserm U1227, Brest university and La Cavale Blanche Hospital, Brest, France., Seror R; Centre for Immunology of Viral Infections and Autoimmune Diseases, Paris-Saclay University Faculty of Medicine, Le Kremlin-Bicetre, France., Fisher B; Institute of Inflammation and Ageing, University Hospitals Birmingham, Birmingham, UK.; Department of Rheumatology, National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Barone F; Institute of Inflammation and Ageing, University Hospitals Birmingham, Birmingham, UK., Bowman SJ; Institute of Inflammation and Ageing, University Hospitals Birmingham, Birmingham, UK., Bombardieri M; Centre for Experimental Medicine and Rheumatology, Queen Mary University of London Faculty of Medicine and Dentistry, London, UK., Lendrem D; Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK., Felten R; Centre National de Référence des maladies auto-immunes et systémiques rares Est/Sud-Ouest (RESO), Hôpitaux universitaires de Strasbourg, Strasbourg, France.; Laboratoire d'Immunologie, Immunopathologie et Chimie Thérapeutique, Institut de Biologie Moléculaire et Cellulaire (IBMC), Strasbourg, France., Gottenberg JE; Centre National de Référence des maladies auto-immunes et systémiques rares Est/Sud-Ouest (RESO), Hôpitaux universitaires de Strasbourg, Strasbourg, France.; Laboratoire d'Immunologie, Immunopathologie et Chimie Thérapeutique, Institut de Biologie Moléculaire et Cellulaire (IBMC), Strasbourg, France., Ng WF; Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK wan-fai.ng@newcastle.ac.uk.; National Institute for Health and Care Research (NIHR), Newcastle Biomedical Research Centre & NIHR Newcastle Clinical Research Facility, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2024 Jan 02; Vol. 83 (1), pp. 88-95. Date of Electronic Publication: 2024 Jan 02.
DOI:	10.1136/ard-2023-224503
Abstrakt:	Objectives: Stratification approaches are vital to address clinical heterogeneity in Sjogren's syndrome (SS). We previously described that the Newcastle Sjogren's Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes. Method: We profiled serum proteins using O-link technology of 180 SS subjects. We used 5 O-link proteomics panels which included a total of 454 unique proteins. Network reconstruction was performed using the ARACNE algorithm, with differential expression estimates overlaid on these networks to reveal the key subnetworks of differential expression. Furthermore, data from a phase III trial of tocilizumab in SS were reanalysed by stratifying patients at baseline using NSST. Results: Our analysis highlights differential expression of chemokines, cytokines and the major autoantigen TRIM21 between the SS subtypes. Furthermore, we observe differential expression of several transcription factors associated with energy metabolism and redox balance namely APE1/Ref-1, FOXO1, TIGAR and BACH1. The differentially expressed proteins were inter-related in our network analysis, supporting the concept that distinct molecular networks underlie the clinical subtypes of SS. Stratification of patients at baseline using NSST revealed improvement of fatigue score only in the subtype expressing the highest levels of serum IL-6. Conclusions: Our data provide clues to the pathways contributing to the glandular and non-glandular manifestations of SS and to potential therapeutic targets for different SS subtypes. In addition, our analysis highlights the need for further exploration of altered metabolism and mitochondrial dysfunction in the context of SS subtypes. Competing Interests: Competing interests: VD-P has undertaken clinical trials and provided consultancy or expert advice in the area of Sjogren’s disease to the following companies: MedImmune, UCB, Abbvie, Sanofi, Novartis and BMS. BF has undertaken consultancy for Novartis, BMS, Servier, Galapagos, Roche, Sanofi and Janssen and received research funding from Janssen, Galapagos, Servier and Celgene. SJB has undertaken consultancy for Novartis, BMS, Iqvia and Janssen and accepted hospitality from Novartis to attend a working dinner at the BSR conference regarding secukinumab in inflammatory arthritis in the last year. MB has received consultancy and/or advisory board fees and/or grant support from GSK, Janssen, Ono Pharmaceutical, Horizon Therapeutics in the last two years. W-FN has undertaken clinical trials and provided consultancy or expert advice in the area of Sjogren’s syndrome to the following companies: GlaxoSmithKline, MedImmune, UCB, Abbvie, Roche, Eli Lilly, Takeda, Resolves Therapeutics, Sanofi, Novartis and BMS. No other potential conflict of interest relevant to this article was reported. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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