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Examining the biolo...
Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome : proteomic and network analysis
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- Berry, Joe Scott (författare)
- Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England.
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- Tarn, Jessica (författare)
- Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England.
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- Casement, John (författare)
- Newcastle Univ, Bioinformat Support Unit, Newcastle Upon Tyne, England.
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- Duret, Pierre-Marie (författare)
- Colmar Civilian Hosp, Dept Rheumatol, Colmar, France.
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- Scott, Lauren (författare)
- Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England.
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- Wood, Karl (författare)
- Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England.
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- Johnsen, Svein-Joar (författare)
- Stavanger Univ Hosp, Dept Rheumatol, Stavanger, Norway.
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- Nordmark, Gunnel (författare)
- Uppsala universitet,Reumatologi
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- Devauchelle-Pensec, Valerie (författare)
- Brest Univ, Lymphocytes B & Autoimmun, Inserm U1227, Brest, France.;Cavale Blanche Hosp, Brest, France.
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- Seror, Raphaele (författare)
- Univ Paris Saclay, INSERM, Ctr Immunol Viral Infect & Autoimmune Dis IMVA, Univ Paris Sud,UMR 1184, Le Kremlin Bicetre, France.
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- Fisher, Benjamin (författare)
- Univ Birmingham, Inst Inflammat & Ageing, Birmingham, England.;Univ Hosp Birmingham NHS Fdn Trust, Natl Inst Hlth Res NIHR, Birmingham Biomed Res Ctr, Dept Rheumatol, Birmingham, England.
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- Barone, Fransesca (författare)
- Univ Birmingham, Inst Inflammat & Ageing, Birmingham, England.
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- Bowman, Simon J. (författare)
- Univ Birmingham, Inst Inflammat & Ageing, Birmingham, England.
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- Bombardieri, Michele (författare)
- Queen Mary Univ London, Ctr Expt Med & Rheumatol, Fac Med & Dent, London, England.
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- Lendrem, Dennis (författare)
- Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England.
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- Felten, Renaud (författare)
- Hop Univ Strasbourg, Ctr Natl Reference Malad Autoimmunes & Syst rares, Est Sud Ouest RESO, Serv Rhumatol, Strasbourg, France.;Inst Biol Mol & Cellulaire IBMC, IBMC, Lab Immunopathol & Chim Therapeut, CNRS,UPR3572, Strasbourg, France.
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- Gottenberg, Jacques-Eric (författare)
- Hop Univ Strasbourg, Ctr Natl Reference Malad Autoimmunes & Syst rares, Est Sud Ouest RESO, Serv Rhumatol, Strasbourg, France.;Inst Biol Mol & Cellulaire IBMC, IBMC, Lab Immunopathol & Chim Therapeut, CNRS,UPR3572, Strasbourg, France.
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- Ng, Wan-Fai (författare)
- Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England.;Newcastle Tyne Hosp NHS Fdn Trust, Natl Inst Hlth & Care Res NIHR, Newcastle Biomed Res Ctr, Newcastle Clin Res Fac, Newcastle Upon Tyne, Northumberland, England.;Newcastle Univ, Newcastle Upon Tyne NE2 4HH, England.
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Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England Newcastle Univ, Bioinformat Support Unit, Newcastle Upon Tyne, England. (creator_code:org_t)
- BMJ Publishing Group Ltd, 2024
- 2024
- Engelska.
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:1, s. 88-95
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Sjogren's Syndrome
- Inflammation
- Patient Reported Outcome Measures
- Autoantibodies
- Autoimmune Diseases
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- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Berry, Joe Scott
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Tarn, Jessica
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Casement, John
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Duret, Pierre-Ma ...
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Scott, Lauren
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Wood, Karl
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visa fler...
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Johnsen, Svein-J ...
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Nordmark, Gunnel
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Devauchelle-Pens ...
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Seror, Raphaele
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Fisher, Benjamin
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Barone, Fransesc ...
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Bowman, Simon J.
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Bombardieri, Mic ...
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Lendrem, Dennis
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Felten, Renaud
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Gottenberg, Jacq ...
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Ng, Wan-Fai
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