ArticleArthritis research & therapy2017
Pre-silencing of genes involved in the electron transport chain (ETC) pathway is associated with responsiveness to abatacept in rheumatoid arthritis.
Article in Arthritis research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Gene expression regulated by abatacept associated with methotrexate and correlation with disease activity in rheumatoid arthritis.PloS one · 2020Trial
- Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint.Journal of translational autoimmunity · 2025Article
- Single-cell dual-omics reveals translational and transcriptional landscapes and regulations in oocytes from ovarian endometriosis patients.Frontiers in endocrinology · 2025Article
- Unveiling the link between lactate metabolism and rheumatoid arthritis through integration of bioinformatics and machine learning.Scientific reports · 2024Article
- Mitochondrial respiratory chain component NDUFA4: a promising therapeutic target for gastrointestinal cancer.Cancer cell international · 2024Review
- Monocyte-derived transcriptomes explain the ineffectiveness of abatacept in rheumatoid arthritis.Arthritis research & therapy · 2024Article
- Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.Frontiers in immunology · 2023Review
- Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search.Rheumatology (Oxford, England) · 2022Review
- Precision Medicine for Rheumatoid Arthritis: The Right Drug for the Right Patient-Companion Diagnostics.Diagnostics (Basel, Switzerland) · 2021Review
- Potential role of mitochondria in synoviocytes.Clinical rheumatology · 2021Review
- Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Effects of Biological Therapies on Molecular Features of Rheumatoid Arthritis.International journal of molecular sciences · 2020Review
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Authors and funding
9 authors.
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Abstract
backgroundIn the current context of personalized medicine, one of the major challenges in the management of rheumatoid arthritis (RA) is to identify biomarkers that predict drug responsiveness. From the European APPRAISE trial, our main objective was to identify a gene expression profile associated with responsiveness to abatacept (ABA) + methotrexate (MTX) and to understand the involvement of this signature in the pathophysiology of RA.
methodsWhole human genome microarrays (4 × 44 K) were performed from a first subset of 36 patients with RA. Data validation by quantitative reverse-transcription (qRT)-PCR was performed from a second independent subset of 32 patients with RA. Gene Ontology and WikiPathways database allowed us to highlight the specific biological mechanisms involved in predicting response to ABA/MTX.
resultsFrom the first subset of 36 patients with RA, a combination including 87 transcripts allowed almost perfect separation between responders and non-responders to ABA/MTX. Next, the second subset of patients 32 with RA allowed validation by qRT-PCR of a minimal signature with only four genes. This latter signature categorized 81% of patients with RA with 75% sensitivity, 85% specificity and 85% negative predictive value. This combination showed a significant enrichment of genes involved in electron transport chain (ETC) pathways. Seven transcripts from ETC pathways (NDUFA6, NDUFA4, UQCRQ, ATP5J, COX7A2, COX7B, COX6A1) were significantly downregulated in responders versus non-responders to ABA/MTX. Moreover, dysregulation of these genes was independent of inflammation and was specific to ABA response.
conclusionPre-silencing of ETC genes is associated with future response to ABA/MTX and might be a crucial key to susceptibility to ABA response.
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