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  • Parodis, Ioannis,1981-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)

Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • Elsevier,2024
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-114365
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-114365URI
  • https://doi.org/10.1016/j.ekir.2024.03.014DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • This work was supported by 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 Institutet. This work has received funding from the Innovative Medicines Initiative (IMI) Joint Undertaking (JU) for the PRECISESADS project (grant number 115565), as well as from the IMI 2 JU for the 3TR project (grant number 831434). The JU receives support from the EU Horizon 2020 research and innovation programme and EFPIA.
  • INTRODUCTION: Current therapeutic management of lupus nephritis (LN) fails to induce long-term remission in over 50% of patients, highlighting the urgent need for additional options.METHODS: We analyzed differentially expressed genes (DEGs) in peripheral blood from patients with active LN (n = 41) and active nonrenal lupus (n = 62) versus healthy controls (HCs) (n = 497) from the European PRECISESADS project (NTC02890121), and dysregulated gene modules in a discovery (n = 26) and a replication (n = 15) set of active LN cases.RESULTS: Replicated gene modules qualified for correlation analyses with serologic markers, and regulatory network and druggability analysis. Unsupervised coexpression network analysis revealed 20 dysregulated gene modules and stratified the active LN population into 3 distinct subgroups. These subgroups were characterized by low, intermediate, and high interferon (IFN) signatures, with differential dysregulation of the "B cell" and "plasma cells/Ig" modules. Drugs annotated to the IFN network included CC-motif chemokine receptor 1 (CCR1) inhibitors, programmed death-ligand 1 (PD-L1) inhibitors, and irinotecan; whereas the anti-CD38 daratumumab and proteasome inhibitor bortezomib showed potential for counteracting the "plasma cells/Ig" signature. In silico analysis demonstrated the low-IFN subgroup to benefit from calcineurin inhibition and the intermediate-IFN subgroup from B-cell targeted therapies. High-IFN patients exhibited greater anticipated response to anifrolumab whereas daratumumab appeared beneficial to the intermediate-IFN and high-IFN subgroups.CONCLUSION: IFN upregulation and B and plasma cell gene dysregulation patterns revealed 3 subgroups of LN, which may not necessarily represent distinct disease phenotypes but rather phases of the inflammatory processes during a renal flare, providing a conceptual framework for precision medicine in LN.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Lindblom, JuliusDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology, Dermatology, and Rheumatology, Karolinska University Hospital, Stockholm, Sweden (författare)
  • Toro-Domínguez, DanielGENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada / Andalusian Regional Government, Granada, Spain, Medical Genomics, Granada, Spain (författare)
  • Beretta, LorenzoReferral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Italy (författare)
  • Borghi, Maria O.Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy; IRCCS, Istituto Auxologico Italiano, Milan, Italy (författare)
  • Castillo, JessicaDepartment of Biomedical Engineering, University of Houston, Houston, Texas, USA (författare)
  • Carnero-Montoro, ElenaGENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada / Andalusian Regional Government, Granada, Spain, Medical Genomics, Granada, Spain (författare)
  • Enman, YvonneDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (författare)
  • Mohan, ChandraDepartment of Biomedical Engineering, University of Houston, Houston, Texas, USA (författare)
  • Alarcón-Riquelme, Marta E.GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada / Andalusian Regional Government, Granada, Spain, Medical Genomics, Granada, Spain; Department of Environmental Medicine, Karolinska Institute, Stockholm, Sweden (författare)
  • 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)
  • Nikolopoulos, DionysisDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology, Dermatology, and Rheumatology, Karolinska University Hospital, Stockholm, Sweden (författare)
  • PRECISESADS Clinical Consortium, - (bidragsgivare)
  • Örebro universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Kidney international reports: Elsevier9:6, s. 1817-18352468-0249

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