Whole-blood transcriptomics identifies a distinct metabolic and inflammatory signature in lupus arthritis compared with rheumatoid arthritis

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Publication Details

Journal
Journal of Autoimmunity
Published
2026-09-16
DOI
https://doi.org/10.1016/j.jaut.2026.103634
Primary Topic
Rheumatoid Arthritis Research and Therapies
Type
article
Field-Weighted Citation Impact
0.00

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article

Whole-blood transcriptomics identifies a distinct metabolic and inflammatory signature in lupus arthritis compared with rheumatoid arthritis

Katerina Chatzidionysiou, Panagiotis Garantziotis, George Sentis, Katerina Chavatza et al.
Journal of Autoimmunity
Rheumatoid Arthritis Research and Therapies
article

Whole-blood transcriptomics identifies a distinct metabolic and inflammatory signature in lupus arthritis compared with rheumatoid arthritis

Katerina Chatzidionysiou, Panagiotis Garantziotis, George Sentis, Katerina Chavatza, Chrysoula Kalantzi, Antigone Pieta, George Βertsias, Dionysis Nikolopoulos, Konstantinos Triantafyllias, Theodora Manolakou, Sofia Flouda, Ioannis Parodis, Noemin Kapsala, Anastasia Filia, Aggelos Banos, Dimitrios T. Boumpas
article en

Abstract

BACKGROUND: Lupus arthritis (LA) is a major determinant of clinical outcomes and treat-to-target strategies in systemic lupus erythematosus (SLE), yet its molecular basis remains elusive. METHODS: Whole-blood RNA sequencing from 170 SLE [67 with active arthritis but quiescent disease in other organs; 42 with only mucocutaneous activity (mcSLE); 61 clinically inactive (iSLE)], 19 active rheumatoid arthritis (RA), and 72 healthy donors. Pathway enrichment, unsupervised WGCNA, deconvolution, k-means clustering, and druggability analyses were applied. RESULTS: Compared to mcSLE, LA patients demonstrated upregulation of ribosome/metabolism, while inflammatory pathways were significantly upregulated in mcSLE. Comparison between LA and RA revealed 769 differentially expressed genes, indicating upregulation of ribosome/metabolism and oxidative phosphorylation (OXPHOS) pathways in LA. Activated NK cells were significantly increased in LA compared to RA and mcSLE. Within SLE patients, interferon pathways were less upregulated in LA. Unsupervised analysis showed LA to be strongly linked to upregulation of "OXPHOS/metabolism" module and downregulation of the "Interferon" module. In contrast, mcSLE and iSLE were associated with "Interferon" and "T-cell" modules, respectively. RA was strongly associated with the "Innate immunity" module. LA patients were categorized into three distinct molecular clusters dominated by OXPHOS/metabolism pathways ("metabolism" cluster; n = 14), inflammatory pathways ("inflammation" cluster; n = 29), and both metabolic and inflammatory pathways ("mixed" cluster; n = 24). Druggability analysis revealed differential anticipated benefit from different compounds for each LA-cluster. CONCLUSIONS: Metabolic -rather than inflammatory-pathways are dominant in LA and may account in part for suboptimal responses to existing therapies. LA encompasses molecular subtypes, characterized by distinct pathophysiologic aberrancies potentially reversible by unique compounds.

Journal of AutoimmunityVol. 164
Karolinska University Hospital (SE), University of Crete (GR), Johannes Gutenberg University Mainz (DE), National and Kapodistrian University of Athens (GR), Academy of Athens (GR), Science for Life Laboratory (SE), Karolinska Institutet (SE), Universitätsklinikum Erlangen (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), Institute of Molecular Biology and Biotechnology (BG)
Nyckelfonden, Åke Wiberg Stiftelse, European Commission, Karolinska Institutet, Svenska Läkaresällskapet, Stiftelsen Konung Gustaf V:s 80-årsfond, Reumatikerförbundet, Alex och Eva Wallströms Stiftelse för Vetenskaplig Forskning och Utbildning, Stiftelsen Professor Nanna Svartz Fond, Ulla och Gustaf af Ugglas Stiftelse, Foundation for Research in Rheumatology, European Research Council, H2020 Marie Skłodowska-Curie Actions, HORIZON EUROPE Marie Sklodowska-Curie Actions
Good health and well-being
Openalex Percentile: Top 11%
Rheumatoid Arthritis Research and Therapies
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