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Background: Recombination signal-binding protein for immunoglobulin kappa J region (RBPJ) is a transcriptional regulator that plays an important role in maintaining immune homeostasis. This study aimed to estimate the expression of RBPJ in rheumatoid arthritis (RA) patients and investigate its relationship with RA., Methods: A total of 83 newly diagnosed RA patients and 70 healthy controls were included. mRNA was extracted from peripheral blood mononuclear cells (PBMCs), and the expression of RBPJ was detected using quantitative real-time PCR (qRT‒PCR). An RA dataset (GSE89408) was obtained from the Gene Expression Omnibus (GEO) database, and RA synovial tissues were divided into two groups. The differentially expressed genes (DEGs) were selected with the "DESeq2" R package., Results: RBPJ expression was lower in RA patients than in health controls and was negatively correlated with the DAS28 score, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR). RA synovial tissues from GSE89408 were classified into RBPJ-low (≤ 25%) and RBPJ-high (≥ 75%) groups according to RBPJ expression, and 562 DEGs were identified. Gene Ontology (GO) enrichment analyses revealed that the DEGs significantly affected the regulation of T cell activation and lymphocyte/mononuclear cell differentiation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most enriched pathways of DEGs were the T cell receptor signaling pathway, Th1/2 and Th17 cell differentiation, the PI3K - Akt signaling pathway and cytokine‒cytokine receptor interaction. CytoHubba Plugin revealed that most of the top 10 genes were involved in osteoclast differentiation, the T cell receptor signaling pathway and cytokine‒cytokine receptor interaction., Conclusions: RBPJ expression was significantly lower in RA patients and negatively correlated with disease activity. GEO dataset analysis demonstrated that RBPJ may be involved in osteoclast differentiation, T cell activation and differentiation, and the T cell receptor signaling pathway. Our research may contribute to understanding the potential mechanisms by which RBPJ regulates T cell differentiation and cytokine‒cytokine receptor interaction in RA patients., (© 2024. The Author(s).)

Nuclear-factor, interleukin 3 regulated (NFIL3) is an immune regulator that plays an essential role in autoimmune diseases. However, the relationship between rheumatoid arthritis (RA) and NFIL3 remains largely unknown. In this study, we examined NFIL3 expression in RA patients and its potential molecular mechanisms in RA. Increased NFIL3 expression levels were identified in peripheral blood mononuclear cells (PBMCs) from 62 initially diagnosed RA patients and 75 healthy controls (HCs) by quantitative real-time PCR (qRT-PCR). No correlation between NFIL3 and disease activity was observed. In addition, NFIL3 expression was significantly upregulated in RA synovial tissues analyzed in the Gene Expression Omnibus (GEO) dataset (GSE89408). Then, we classified synovial tissues into NFIL3-high (≥75%) and NFIL3-low (≤25%) groups according to NFIL3 expression levels. Four hundred five differentially expressed genes (DEGs) between the NFIL3-high and NFIL3-low groups were screened out using the "limma" R package. Enrichment analysis showed that most of the enriched genes were primarily involved in the TNF signaling pathway via NFκB, IL-17 signaling pathway, and rheumatoid arthritis pathways. Then, 10 genes (IL6, IL1β, CXCL8, CCL2, PTGS2, MMP3, MMP1, FOS, SPP1, and ADIPOQ) were identified as hub genes, and most of them play a key role in RA. Positive correlations between the hub genes and NFIL3 were revealed by qRT-PCR in RA PBMCs. An NFIL3-related protein-protein interaction (PPI) network was constructed using the STRING database, and four clusters (mainly participating in the inflammatory response, lipid metabolism process, extracellular matrix organization, and circadian rhythm) were constructed with MCODE in Cytoscape. Furthermore, 29 DEGs overlapped with RA-related genes from the RADB database and were mainly enriched in IL-17 signaling pathways. Thus, our study revealed the elevated expression of NFIL3 in both RA peripheral blood and synovial tissues, and the high expression of NFIL3 correlated with the abnormal inflammatory cytokines and inflammatory responses, which potentially contributed to RA progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Zheng, Chen, Wang, Pu, Yu, Yan, Chen, Wang, Shen, Li and Pan.)

The relationship among the gut microbiome, global fecal metabolites and rheumatoid arthritis (RA) has not been systematically evaluated. In this study, we performed 16S rDNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based nontargeted metabolomic profiling on feces of 26 untreated RA patients and 26 healthy controls. Twenty-six genera and forty-one MS2-identified metabolites were significantly altered in the RA patients. Klebsiella , Escherichia , Eisenbergiella and Flavobacterium were more abundant in the RA patients, while Fusicatenibacter , Megamonas and Enterococcus were more abundant in the healthy controls. Function prediction analysis demonstrated that the biosynthesis pathways of amino acids, such as L-arginine and aromatic amino acids, were depleted in the RA group. In the metabolome results, fecal metabolites including glycerophospholipids (PC(18:3(9Z,12Z,15Z)/16:1(9Z)), lysoPE 19:1, lysoPE 18:0, lysoPC(18:0/0:0)), sphingolipids (Cer(d18:0/16:0), Cer(d18:0/12:0), Cer(d18:0/14:0)), kynurenic acid, xanthurenic acid and 3-hydroxyanthranilic acid were remarkably altered between the RA patients and healthy controls. Dysregulation of pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism and glycerophospholipid metabolism, may contribute to the development of RA. Additionally, we revealed that the gut microbiome and metabolites were interrelated in the RA patients, while Escherichia was the core genus. By depicting the overall landscape of the intestinal microbiome and metabolome in RA patients, our study could provide possible novel research directions regarding RA pathogenesis and targeted therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Du, Pu, Zheng, Chen, Wang, Li, Chen, Pan and Shen.)

Background: FURIN belongs to the proprotein convertase family that processes proproteins and is involved in many diseases. However, the role of FURIN in rheumatoid arthritis (RA) remains unknown. In this study, we investigated the association between circulating FURIN and disease activity in patients with RA and the effect of FURIN in THP-1-derived macrophages., Methods: A total of 108 RA patients and 39 healthy controls participants were included in this study. RA patients were divided into four disease activity groups determined by the Disease Activity Score of 28 joints (DAS28). FURIN expression in peripheral blood mononuclear cells (PBMCs) and serum was detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Western blotting and qRT-PCR were used to detect cytokines level after interfering FURIN expressed in THP-1-derived macrophages., Results: Both FURIN mRNA and protein levels were significantly higher in RA patients than in healthy controls participants (P < .001). No significant difference in FURIN expression was observed among the four RA groups (P > .05). Spearman correlation revealed that FURIN positively correlated with transforming growth factor-β1(TGF-β1), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP). Moreover, the inhibition of FURIN in THP-1-derived macrophages promoted the caspase-1 and IL-1β expression (P < .05)., Conclusion: FURIN levels were significantly increased in the peripheral blood of RA patients and were not associated with disease activity. The inhibition of FURIN in THP-1-derived macrophages with elevated IL-1β levels shows that FURIN may have an anti-inflammatory effect., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Aim: Data from 124 rheumatoid arthritis (RA) patients and 69 healthy controls were collected. Materials & methods: ELISA was performed to detect serum FABP4 levels. Results: FABP4 level was elevated in RA patients and positively associated with 28-joint disease activity score, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, total cholesterol, triglyceride and low-density lipoprotein cholesterol. Additionally, the area under the receiver operating characteristic curve for FABP4 was 0.685 for RA patients versus healthy controls (p = 0.001). RA patients were separated into low, moderate and high disease activity based on 28-joint disease activity score. The area under the receiver operating characteristic value was 0.877 for RA patients with high disease activity versus healthy controls (p < 0.001). Conclusion: FABP4 was associated with disease activity in RA patients.

Objective: Reactive oxygen species are believed to be involved in the onset of RA, and the association between nuclear-encoded mitochondrial respiratory chain-related variants and RA has recently been revealed. However, little is known about the landscape of mitochondrial DNA (mtDNA) variants in RA., Methods: Next-generation sequencing was conducted to profile mtDNA germline and somatic variants in 124 RA patients and 123 age- and sex-matched healthy controls in the Taizhou area, China. Fisher's exact test, SKAT and SKAT-O were used for gene-burden tests to investigate RA-related variants of mitochondrial genes. Predictive tools were applied to evaluate the pathogenicity of mtDNA variants, and mtDNA haplogroups were assigned according to mtDNA mutations recorded in PhyloTree database. The frequency distribution of mtDNA haplogroups between the groups was compared using χ2 analysis., Results: We identified 467 RA-unique and 341 healthy control-unique mtDNA variants, with 443 common variants. Only MT-ATP6 with a significant burden of variants was identified by Fisher's exact test, SKAT and SKAT-O, even after Bonferroni adjustment, and the enrichment variants in MT-ATP6 was mainly driven by m.8830C>A, m.8833G>C and m.8843T>A variants. Besides, four frequently low-heteroplasmic variants including the three variants above and m.14135T>G of MT-ND5 were detected in RA only; except for m.8830C>A, they are considered potential pathogenicity based on functional predictions. χ2 analysis before Bonferroni adjustment revealed haplogroup F1/F1a to be negatively associated with RA (P < 0.05)., Conclusion: These results profiled the landscape of germline and somatic mtDNA variants in RA and supported the effects of mitochondrial genes on RA., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Recently, clinical studies have described an association between albumin and the derived neutrophil to lymphocyte ratio (dNLR) with several diseases. This study was aimed to investigate the albumin-dNLR (ALB-dNLR) score in rheumatoid arthritis (RA) patients and assess its relationship with clinical and laboratory parameters of RA., Methods: We retrospectively enrolled 127 RA patients, 155 osteoarthritis (OA) patients, and 155 healthy controls. The ALB-dNLR score was based on serum albumin level, neutrophil count, and white cell count. The Spearman's rank test was used to measure the correlations between ALB-dNLR score and disease activity as well as laboratory indexes., Results: The ALB-dNLR score was significantly higher in RA patients than in OA patients (P < 0.001) and in healthy controls (P < 0.001). The proportion of higher ALB-dNLR score has been raised along with increased disease activity (P < 0.001). The Spearman's rank test showed that ALB-dNLR score was positively associated with DAS28 score, CRP, ESR, IgA, and platelet count. Moreover, the receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of ALB-dNLR was 0.693 (95% CI: 0.631-0.755), which was higher than that of albumin (AUC: 0.625, 95% CI: 0.559-0.692) and dNLR (AUC: 0.680, 95% CI: 0.617-0.743) alone., Conclusions: The results demonstrate that the ALB-dNLR score increased in RA patients. The ALB-dNLR score may be a useful marker to estimate the disease activity of RA patients., (© 2018 Wiley Periodicals, Inc.)

Toll-like receptor (TLR) 10, mainly expressed on B cells, has emerged as a modulatory receptor in inflammation. Nonetheless, the clinical significance of TLR10 in rheumatoid arthritis (RA) remains unclear. In this study, we explored the expression of TLR10 in B cells and B cell subsets in RA subjects and healthy controls (HCs) and determined its relevance to disease activity and inflammatory biomarkers. TLR10 levels in B cells and B cell subsets (CD19 + CD27 + , CD19 + CD27 - , CD27 + IgD - , CD27 + IgD + , CD27 - IgD + , D27 - IgD - , CD19 + CD5 + , and CD19 + CD5 - ) and inflammatory biomarker concentrations in peripheral blood (PB) obtained from RA subjects and HCs were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations of TLR10 expression with disease activity and inflammatory biomarkers were then analysed. Similar levels of TLR10 in all CD19 + B cells were observed in the RA subjects and HCs. Compared to that in the HCs, TLR10 was elevated significantly in the CD19 + CD27 - IgD - and CD19 + CD5 + subsets in the RA subjects. In addition, almost all subsets expressing TLR10 were increased with disease activity. The present study reveals that enhanced TLR10 in B cell subsets is positively correlated with disease activity in RA subjects.

The lymphocyte-monocyte ratio (LMR) is a systemic inflammatory marker for prediction of disease development, progress, and survival. Recently, a genome-wide association study identified genetic variations in ITGA4 and HLA-DRB1 that affect the LMR levels and were widely believed to be susceptibility genes for autoimmune diseases, including rheumatoid arthritis (RA). However, the role of LMR in RA patients remains unclear. The LMR level and other laboratory data of 66 RA patients, 163 osteoarthritis (OA) patients, and 131 healthy controls (HC) were compared using binary logistic regression. The correlations between LMR and disease activity and other inflammatory markers were measured using the Spearman rank test. ROC curve analyses assessed the diagnostic accuracy of LMR in RA. The LMR and lymphocyte count were significantly lower in RA patients, whereas the monocyte count was significantly higher relative to the HC group/OA patients (p < 0.01). A decreased LMR has been associated with increased disease activity (p = 0.012). In addition, the DAS28 and traditional inflammatory markers, including ESR, CRP, RDW, PLR, and NLR, and immune-related factors, such as C4, IgA, and IgM, were inversely correlated with LMR, while hemoglobin and albumin were positively correlated with LMR. The ROC curve showed that the area under the curve of LMR was 0.705 (95%CI = 0.630-0.781). The corresponding specificity and sensitivity were 82.82 and 45.45%, respectively. The present study shows that the LMR is an important inflammatory marker which could be used to identify disease activity in RA patients and to distinguish RA from OA patients.