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Molecular character...
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Parodis, Ioannis,1981-Karolinska Institutet,Örebro universitet,Institutionen för medicinska vetenskaper,Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden ; Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
(författare)
Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort
- Artikel/kapitelEngelska2024
Förlag, utgivningsår, omfång ...
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HighWire Press,2024
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:oru-111801
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-111801URI
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https://doi.org/10.1136/ard-2023-224795DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:155137370URI
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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IP has received grants from the Swedish Rheumatism Association (R-969696), King Gustaf V’s 80-year Foundation (FAI-2020-0741), Swedish Society of Medicine (SLS-974449), Nyckelfonden (OLL-974804), Professor Nanna Svartz Foundation (2021-00436), Ulla and Roland Gustafsson Foundation (2021-26), Region Stockholm (FoUI-955483), and Karolinska Institute. This work was supported by EU/EFPIA/Innovative Medicines Initiative (IMI) Joint Undertaking (JU) PRECISESADS grant no. 115565 and IMI 2 JU (now HIH) 3TR grant no. 831434, and Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy, EXC 2155, project no. 390874280.
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OBJECTIVES: To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE).METHODS: We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission.RESULTS: We analysed data from 321 patients; 40.8% were in LLDAS, and 17.4% in DORIS remission. After exclusion of patients in remission, 28.3% were in LLDAS. Overall, 604 pathways differed significantly in LLDAS versus non-LLDAS patients with an false-discovery rate-corrected p (q)<0.05 and a robust effect size (dr)≥0.36. Accordingly, 288 pathways differed significantly between DORIS remitters and non-remitters (q<0.05 and dr≥0.36). DEPs yielded distinct molecular clusters characterised by differential serological, musculoskeletal, and renal activity. Analysis of partially overlapping samples showed no DEPs between LLDAS and DORIS remission. Drug repurposing potentiality for treating SLE was unveiled, as were important pathways underlying active SLE whose modulation could aid attainment of LLDAS/remission, including toll-like receptor (TLR) cascades, Bruton tyrosine kinase (BTK) activity, the cytotoxic T lymphocyte antigen 4 (CTLA-4)-related inhibitory signalling, and the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome pathway.CONCLUSIONS: We demonstrated for the first time molecular signalling pathways distinguishing LLDAS/remission from active SLE. LLDAS/remission was associated with reversal of biological processes related to SLE pathogenesis and specific clinical manifestations. DEP clustering by remission better grouped patients compared with LLDAS, substantiating remission as the ultimate treatment goal in SLE; however, the lack of substantial pathway differentiation between the two states justifies LLDAS as an acceptable goal from a biological perspective.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lindblom, JuliusKarolinska Institutet
(författare)
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Barturen, GuillermoGENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada / Andalusian Regional Government, Granada, Spain, Medical Genomics, Granada, Spain; Department of Genetics, Faculty of Sciences, University of Granada, Granada, Spain
(författare)
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Ortega-Castro, RafaelaServicio Andaluz de Salud, Hospital Universitario Reina Sofía, Cordoba, Spain
(författare)
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Cervera, RicardDepartment of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain
(författare)
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Pers, Jacques-OlivierCentre Hospitalier Universitaire de Brest, Hopital de la Cavale Blanche, Brest, France
(författare)
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Genre, FernandaResearch Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, Spain
(författare)
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Hiepe, FalkCharité Universitätsmedizin Berlin, Berlin, Germany
(författare)
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Gerosa, MariaUniversità degli studi di Milano, Milan, Italy
(författare)
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Kovács, LászlóUniversity of Szeged, Szeged, Hungary
(författare)
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De Langhe, EllenKatholieke Universiteit Leuven and Universitair Ziekenhuis Leuven, Leuven, Belgium
(författare)
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Piantoni, SilviaRheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, Azienda Socio Sanitaria Territoriale Spedali Civili and University of Brescia, Brescia, Italy
(författare)
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Stummvoll, GeorgMedical University of Vienna, Vienna, Austria
(författare)
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Vasconcelos, CarlosCentro Hospitalar do Porto, Porto, Portugal
(författare)
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Vigone, BarbaraFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
(författare)
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Witte, TorstenHannover Medical School, Hannover, Germany
(författare)
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Alarcón-Riquelme, Marta E.Karolinska Institutet
(författare)
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Beretta, LorenzoFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
(författare)
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PRECISESADS Clinical Consortium, -
(bidragsgivare)
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Örebro universitetInstitutionen för medicinska vetenskaper
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Annals of the Rheumatic Diseases: HighWire Press83:7, s. 889-9000003-49671468-2060
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Parodis, Ioannis ...
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Lindblom, Julius
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Ortega-Castro, R ...
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Cervera, Ricard
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Pers, Jacques-Ol ...
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Genre, Fernanda
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Hiepe, Falk
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Gerosa, Maria
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Kovács, László
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De Langhe, Ellen
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Piantoni, Silvia
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Stummvoll, Georg
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Vasconcelos, Car ...
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Vigone, Barbara
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Witte, Torsten
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Beretta, Lorenzo
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