scholarly journals The macrophage reprogramming ability of antifolates reveals soluble CD14 as a potential biomarker for methotrexate response in rheumatoid arthritis

2021 ◽  
Author(s):  
Sara Fuentelsaz-Romero ◽  
Celia Barrio Alonso ◽  
Raquel Garcia Campos ◽  
Monica Torres Torresano ◽  
Ittai Muller ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Monocyte ◽  
Serum Levels ◽  
Gene Signature ◽  
Soluble Cd14 ◽  
Potential Biomarker ◽  
Exogenous Addition ◽  
Proinflammatory Gene ◽  
One Carbon Metabolism ◽  
The One

The physio-pathological relevance of the one-carbon metabolism (OCM) is illustrated by the chemotherapeutic and anti-inflammatory effects of the antifolates Pemetrexed (PMX) and Methotrexate (MTX) in cancer and rheumatoid arthritis (RA). We report that OCM determines the functional and gene expression profile of human macrophages. PMX induces the acquisition of a p53-dependent proinflammatory gene signature in human monocyte-derived macrophages (GM-Mθ). Indeed, OCM blockade reprograms GM-Mθ towards a state of LPS-tolerance at the signaling and functional levels, an effect abolished by folinic acid. Importantly, OCM blockade led to reduced expression of membrane-bound and soluble CD14 (sCD14), whose exogenous addition restores LPS sensitivity. The therapeutic relevance of these results was confirmed in early RA patients, as MTX-responder RA patients exhibit lower sCD14 serum levels, with baseline sCD14 levels predicting MTX response. Our results indicate that OCM is a metabolic circuit that critically mediates the acquisition of innate immune tolerance, and positions sCD14 as a valuable tool to predict MTX-response in RA patients.

scholarly journals Circulating miRNA-125b Is a Potential Biomarker Predicting Response to Rituximab in Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Isabelle Duroux-Richard ◽  
Yves-Marie Pers ◽  
Sylvie Fabre ◽  
Meryem Ammari ◽  
Dominique Baeten ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Predictive Value ◽  
Predictive Biomarker ◽  
Serum Levels ◽  
High Serum ◽  
Response To Treatment ◽  
Serum Samples ◽  
Total Blood ◽  
Novel Mirna ◽  
Potential Biomarker

Although biologic therapies have changed the course of rheumatoid arthritis (RA), today’s major challenge remains to identify biomarkers to target treatments to selected patient groups. Circulating micro(mi)RNAs represent a novel class of molecular biomarkers whose expression is altered in RA. Our study aimed at quantifying miR-125b in blood and serum samples from RA patients, comparing healthy controls and patients with other forms of rheumatic diseases and arthritis, and evaluating its predictive value as biomarker for response to rituximab. Detectable levels of miR-125b were measured in total blood and serum samples and were significantly elevated in RA patients compared to osteoarthritic and healthy donors. The increase was however also found in patients with other forms of chronic inflammatory arthritis. Importantly, high serum levels of miR-125b at disease flare were associated with good clinical response to treatment with rituximab three months later (P=0.002). This predictive value was not limited to RA as it was also found in patients with B lymphomas. Our results identify circulating miR-125b as a novel miRNA over expressed in RA and suggest that serum level of miR-125b is potential predictive biomarker of response to rituximab treatment.

scholarly journals Serum Level of Endothelial Cell-Specific Molecule -1 (ESM -1) as a New Potential Biomarker for Rheumatoid Arthritis Disease Activity

2018 ◽  
Vol 12 (1) ◽  
pp. 189-196
Author(s):  
Noha Abdelsalam ◽  
Ashraf Hussein Mohamed ◽  
Sameh Abdellatif ◽  
Eslam Eid ◽  
Ehsan Mohamed Rizk ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Cell ◽  
Disease Activity ◽  
Severe Disease ◽  
Serum Levels ◽  
Control Group ◽  
Cross Sectional ◽  
Das 28 ◽  
Rheumatoid Arthritis Disease ◽  
Potential Biomarker

Background:Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by destruction of the joint cartilage and bone. Endothelial dysfunction (ED) in RA may be related to disease activity. Our objective is to explore serum levels of endothelial cell-specific molecule-1 (ESM-1) as a biomarker for RA disease activity.Methods:A cross-sectional study was carried out and included 83 adult patients with RA, in addition to 20 healthy subjects (age and sex-matched) as a control group. Based on Disease Activity Score in 28 joints (DAS-28), the patient's group was subdivided into four subgroups(remission, mild, moderate and severe disease activity state). The demographic & clinical data, BMI, DAS-28 and Serological assessment [Erythrocyte Sedimentation Rate (ESR), CRP, Rheumatoid Factor (RF) and Anti-Citrullinated Peptide Antibody (ACPA)] were recorded. ESM-1was assayed for all participants.Results:Serum levels of ESM1 were significantly higher in the patient group than the control group (P< 0.0001). ESM-1 serum levels were significantly higher in patients with severe disease activity subgroup compared with patients with remission and mild disease activity subgroups (P< 0.0001). ESM-1 was positively and significantly correlated with DAS-28 score, The Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Larsen score (P= 0.002, 0.0001 & 0.0001 respectively).Conclusion:ESM-1 could be a biomarker for RA disease activity.

scholarly journals LXR nuclear receptors prompt a pro-inflammatory gene and functional profile in human macrophages

2021 ◽  
Author(s):  
Arturo González de la Aleja1 ◽  
Mónica Torres-Torresano ◽  
Juan Vladimir de la Rosa ◽  
Barbara Alonso ◽  
Enrique Capa-Sardón ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Cholesterol Metabolism ◽  
Macrophage Polarization ◽  
Human Monocyte ◽  
Gene Signature ◽  
Human Macrophage ◽  
Human Macrophages ◽  
Inflammatory Gene ◽  
Anti Inflammatory

Abstract Liver X Receptors (LXR) control cholesterol metabolism and exert anti-inflammatory actions in activated macrophages. However, their contribution to human macrophage polarization in the absence of pathogenic stimuli remains unclear. In fact, the LXR pathway has been reported to be significantly enriched in pro-inflammatory synovial macrophages from rheumatoid arthritis patients as well as in immunosuppressive tumors-associated macrophages from human metastatic colon tumors. To determine the role of LXR on macrophage differentiation and polarization, we have analyzed the contribution of LXR to the acquisition of the inflammatory and T-cell-activating functions of human monocyte-derived macrophages. We now report that LXR activation prompts the acquisition of a pro-inflammatory gene signature in human macrophages, whereas LXR inactivation results in enrichment of an anti-inflammatory gene profile. Accordingly, activation and inhibition of LXR oppositely alter the production of cytokines (e.g., TNF, IL1b, CCL17, CCL19, IFNb1) and T cell stimulation activities associated to human macrophage polarization. Mechanistically, the LXR-stimulated macrophage polarization shift relies on their ability to modulate the expression of MAFB and MAF, which govern the acquisition of the macrophage anti-inflammatory profile. The pathological significance of the LXR-mediated macrophage polarization shift was demonstrated by the ability of LXR agonists to modulate macrophage polarization promoted by either tumor-derived ascitic fluids or by synovial fluid from rheumatoid arthritis patients. As a whole, our results demonstrate that LXR activation prompts the acquisition of a pro-inflammatory transcriptional and functional specialization in human macrophages .

scholarly journals Galectin-1: a Potential Biomarker Differentiating Between Early Rheumatoid Arthritis and Spondyloarthritis

2021 ◽  
Author(s):  
Ana Triguero-Martínez ◽  
Emilia Roy-Vallejo ◽  
Eva Tomero ◽  
Nuria Montes ◽  
Hortensia de la fuente ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Inflammatory Diseases ◽  
Serum Levels ◽  
Clinical Parameters ◽  
Diagnostic Biomarker ◽  
Serum Samples ◽  
Healthy Donors ◽  
Potential Biomarker ◽  
Fluid Levels

Abstract Background: Galectin 1 (Gal1) is a lectin highly expressed in immune cells that plays a key immunoregulatory role in autoimmunity and resolution of chronic inflammation. Immune-mediated inflammatory diseases (IMIDs) are a broad group of disorders that share pathogenic mechanisms involving components of acquired and innate immunity. Although IMIDs can develop at onset similar features such as peripheral arthritis, they show differences in their evolution and response to treatments. Therefore, additional diagnostic biomarkers are needed in order to get a better classification of patients with early arthritis, especially those not fulfilling specific classification criteria. In this regard, we have recently described that Gal1 serum levels are increased in rheumatoid arthritis (RA) patients compared to healthy donors (HD). Thus, the objective of this work was to evaluate Gal1 levels in serum and synovial fluid from spondyloarthritis (SpA) patients in comparison with RA patients in order to determine their value as a diagnostic biomarker.Methods: We studied Gal1 levels in serum samples from SpA (n=55) and RA patients (n=52). In addition, 49 HD were studied. We also measured Gal1 synovial fluid levels in RA (n=26), osteoarthritis (OA) (n=26) and peripheral SpA (n=26). In SpA patients, clinical parameters were also collected in order to evaluate their association with Gal1 serum levels. Results: We found that SpA patients showed significantly lower Gal1 serum levels than RA patients and similar levels to the general population. In SpA patients, Gal1 synovial fluid levels were similar to those of OA patients and significantly lower than in RA patients. In addition, we did not find any correlation between Gal1 serum levels and clinical parameters of severity in SpA patients.Conclusions: Our results suggest that Gal1 might be a potential diagnostic biomarker of RA that could allow distinguishing between SpA and RA patients.

scholarly journals The activation fragment of PAR2 is elevated in serum from patients with rheumatoid arthritis and reduced in response to anti-IL6R treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefania Kalogera ◽  
Yi He ◽  
Anne-Christine Bay-Jensen ◽  
Thorbjørn Gantzel ◽  
Shu Sun ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Serine Proteases ◽  
Serum Levels ◽  
Cartilage Destruction ◽  
Synovial Hyperplasia ◽  
Amino Acid Peptide ◽  
Potential Biomarker ◽  
Protease Activated Receptor 2 ◽  
Inter Assay Variation

AbstractOsteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and pain. PAR2 is activated via cleavage of its N-terminus by serine proteases. In this study a competitive ELISA assay was developed targeting the 36-amino acid peptide that is cleaved and released after PAR2 activation (PRO-PAR2). Technical assay parameters including antibody specificity, intra- and inter-assay variation (CV%), linearity, accuracy, analyte stability and interference were evaluated. PRO-PAR2 release was confirmed after in vitro cleavage of PAR2 recombinant protein and treatment of human synovial explants with matriptase. Serum levels of 22 healthy individuals, 23 OA patients and 15 RA patients as well as a subset of RA patients treated with tocilizumab were evaluated. The PRO-PAR2 antibody was specific for the neo-epitope and intra-inter assay CV% were 6.4% and 5.8% respectively. In vitro cleavage and matriptase treated explants showed increased PRO-PAR2 levels compared to controls. In serum, PRO-PAR2 levels were increased in RA patients and decreased in RA patients treated with tocilizumab. In conclusion, PRO-PAR2 may be a potential biomarker for monitoring RA disease and pharmacodynamics of treatment.

Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Functional Disability ◽  
Serum Levels ◽  
Amplification Refractory Mutation System ◽  
Reactive Protein ◽  
Tnf Α ◽  
Mutation System ◽  
Potential Factor ◽  
Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

Effect of Dietary Education on Cardiovascular risk Factors in Rheumatoid Arthritis Patients

2020 ◽  
Vol 16 ◽  
Author(s):  
Rahil Taheri ◽  
Shahram Molavynejad ◽  
Parvin Abedi ◽  
Elham Rajaei ◽  
Mohammad Hosein Haghighizadeh
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Statistical Tests ◽  
Intervention Group ◽  
Serum Levels ◽  
Control Group ◽  
Dietary Education

Aim: The aim of this study was to investigate the effect of dietary education on cardiovascular risk factors in patients with rheumatoid arthritis. Method: In this randomized clinical trial, 112 patients with rheumatoid arthritis were randomly assigned into two groups, intervention and control. Dietary education was provided for the intervention group in 4 sessions; anthropometric measurements, serum levels of RF, triglycerides, cholesterol, HDL, LDL, and fasting blood sugar were measured before and three months after intervention. Data was analyzed using SPSS software and appropriate statistical tests. Results: The mean of total cholesterol (p <0.001), triglycerides (p = 0.004), LDL (p <0.001), systolic blood pressure (p = 0.001), diastolic blood pressure (p = 0.003), FBS and BMI (p <0.001) were decreased significantly in the intervention group after education compared the control group. Conclusion: Traditional care for rheumatoid arthritis patients is not enough. Patients need more education in order to improve their situation.

scholarly journals Serum IL-35 is decreased in overweight patients with rheumatoid arthritis: its correlation with Th1/Th2/Th17-related cytokines

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuxuan Li ◽  
Yang Jie ◽  
Xiaofei Wang ◽  
Jing Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Medical Records ◽  
Clinical Information ◽  
Serum Cytokines ◽  
Healthy Donors ◽  
Potential Biomarker ◽  
Tnf Α ◽  
Ifn Γ ◽  
Quantitative Changes ◽  
Anti Inflammatory Cytokine

Abstract Background Obesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA. Results The serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI. Conclusions Quantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.

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