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Interferon and B-ce...
Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis
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- Parodis, Ioannis, 1981- (author)
- 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
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- Lindblom, Julius (author)
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology, Dermatology, and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
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- Toro-Domínguez, Daniel (author)
- GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada / Andalusian Regional Government, Granada, Spain, Medical Genomics, Granada, Spain
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- Beretta, Lorenzo (author)
- Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Italy
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- Borghi, Maria O. (author)
- Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy; IRCCS, Istituto Auxologico Italiano, Milan, Italy
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- Castillo, Jessica (author)
- Department of Biomedical Engineering, University of Houston, Houston, Texas, USA
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- Carnero-Montoro, Elena (author)
- GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada / Andalusian Regional Government, Granada, Spain, Medical Genomics, Granada, Spain
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- Enman, Yvonne (author)
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
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- Mohan, Chandra (author)
- Department of Biomedical Engineering, University of Houston, Houston, Texas, USA
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- Alarcón-Riquelme, Marta E. (author)
- 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
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- Barturen, Guillermo (author)
- GENYO, 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
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- Nikolopoulos, Dionysis (author)
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology, Dermatology, and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
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PRECISESADS Clinical Consortium, - (contributor)
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(creator_code:org_t)
- Elsevier, 2024
- 2024
- English.
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In: Kidney international reports. - : Elsevier. - 2468-0249. ; 9:6, s. 1817-1835
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Biologics
- druggability
- lupus nephritis
- precision medicine
- systemic lupus erythematosus
- trancriptomics
- transcriptome
Publication and Content Type
- ref (subject category)
- art (subject category)
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Parodis, Ioannis ...
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Lindblom, Julius
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Toro-Domínguez, ...
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Beretta, Lorenzo
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Borghi, Maria O.
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Castillo, Jessic ...
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Carnero-Montoro, ...
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Enman, Yvonne
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Mohan, Chandra
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Alarcón-Riquelme ...
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Barturen, Guille ...
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Nikolopoulos, Di ...
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PRECISESADS Clin ...
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- MEDICAL AND HEALTH SCIENCES
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Kidney internati ...
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Örebro University