{"title":"Upregulation of TNF-α and IL-6 in palindromic rheumatism: A biomarker link to rheumatoid arthritis progression and therapeutic implications","authors":"Kamran Javidi-Aghdam , Mostafa Akbarzadeh-Khiavi , Sepideh Parvizpour , Shima Rahmani , Faranak Sheikhmonazzah , Ata Khodaparast , Aida Malek Mahdavi , Azam Safary , Alireza Khabbazi","doi":"10.1016/j.genrep.2025.102175","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Palindromic rheumatism (PR) is a rare autoimmune disease characterized by episodic joint inflammation, often progressing to rheumatoid arthritis (RA). However, the molecular mechanisms driving this transition remain unclear. This study aimed to investigate the roles of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the PR progression toward RA by examining their serum levels and gene expression in patients with PR and RA, compared to healthy controls (HCs).</div></div><div><h3>Methods</h3><div>This cross-sectional study was conducted on peripheral blood mononuclear cells (PBMCs) obtained from patients with PR (<em>n</em> = 17), RA (<em>n</em> = 35), and age-sex-matched HCs (<em>n</em> = 38). TNF-α and IL-6 serum levels were quantified using enzyme-linked immunosorbent assay, and mRNA levels were analyzed through real-time PCR. Classification and regression tree (CART) models were employed to determine the relevance of these cytokines in RA.</div></div><div><h3>Results</h3><div>TNF-α serum levels in PR, RA, and HCs were measured at 10.5 ± 1.3, 8.9 ± 1.1, and 6.3 ± 0.8 pg/mL, respectively. IL-6 levels were 6.84 ± 2.6, 6.65 ± 2.5, and 1.10 ± 0.5 pg/mL for the same groups. Both cytokines were significantly elevated in PR and RA patients compared to HCs (<em>p</em> < 0.05). Gene expression analysis confirmed the upregulation of TNF-α and IL-6 in both the PR and RA groups.</div></div><div><h3>Conclusions</h3><div>These findings suggest that the upregulation of TNF-α and IL-6 may be key factors driving the progression of PR to RA. Targeting these cytokines could represent a novel therapeutic strategy to prevent disease advancement.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"39 ","pages":"Article 102175"},"PeriodicalIF":1.0000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452014425000482","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Palindromic rheumatism (PR) is a rare autoimmune disease characterized by episodic joint inflammation, often progressing to rheumatoid arthritis (RA). However, the molecular mechanisms driving this transition remain unclear. This study aimed to investigate the roles of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the PR progression toward RA by examining their serum levels and gene expression in patients with PR and RA, compared to healthy controls (HCs).
Methods
This cross-sectional study was conducted on peripheral blood mononuclear cells (PBMCs) obtained from patients with PR (n = 17), RA (n = 35), and age-sex-matched HCs (n = 38). TNF-α and IL-6 serum levels were quantified using enzyme-linked immunosorbent assay, and mRNA levels were analyzed through real-time PCR. Classification and regression tree (CART) models were employed to determine the relevance of these cytokines in RA.
Results
TNF-α serum levels in PR, RA, and HCs were measured at 10.5 ± 1.3, 8.9 ± 1.1, and 6.3 ± 0.8 pg/mL, respectively. IL-6 levels were 6.84 ± 2.6, 6.65 ± 2.5, and 1.10 ± 0.5 pg/mL for the same groups. Both cytokines were significantly elevated in PR and RA patients compared to HCs (p < 0.05). Gene expression analysis confirmed the upregulation of TNF-α and IL-6 in both the PR and RA groups.
Conclusions
These findings suggest that the upregulation of TNF-α and IL-6 may be key factors driving the progression of PR to RA. Targeting these cytokines could represent a novel therapeutic strategy to prevent disease advancement.
Gene ReportsBiochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
7.70%
发文量
246
审稿时长
49 days
期刊介绍:
Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.