Circulating Dickkopf-1 Is Correlated with Bone Erosion and Inflammation in Rheumatoid Arthritis

2011 ◽  
Vol 38 (5) ◽  
pp. 821-827 ◽  
Author(s):  
SHI-YAO WANG ◽  
YAN-YING LIU ◽  
HUA YE ◽  
JIAN-PING GUO ◽  
RU LI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Bone Erosion ◽  
Interleukin 1 ◽  
Healthy Controls ◽  
Serum Samples ◽  
Reactive Protein ◽  
Tnf Α ◽  
Factor Α ◽  
Dickkopf 1

Objective.To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA.Methods.Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA.Results.The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10−4) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-α inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01).Conclusion.DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.

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.

Levels of Plasma-soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) Are Correlated with Disease Activity in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 933-938 ◽  
Author(s):  
SANG TAE CHOI ◽  
EUN-JIN KANG ◽  
YOU JUNG HA ◽  
JUNG-SOO SONG
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Myeloid Cells ◽  
Disease Status ◽  
Joint Disease ◽  
Healthy Controls ◽  
Cell Counts ◽  
Tnf Α ◽  
White Blood Cell Counts ◽  
Factor Α

Objective.To determine whether levels of plasma-soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are elevated in patients with rheumatoid arthritis (RA) and whether levels are correlated with disease activity and other variables.Methods.Our study included 71 patients with RA and 50 age- and sex-matched healthy controls. Clinical characteristics and laboratory measures, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and 28-joint Disease Activity Score (DAS28) were assessed. Plasma levels of sTREM-1 and tumor necrosis factor-α (TNF-α) were measured by ELISA.Results.Patients with RA had significantly higher plasma sTREM-1 levels than healthy controls (170.10 ± 84.71 pg/ml vs 97.41 ± 40.64 pg/ml; p < 0.001). In patients with RA, plasma sTREM-1 levels were found to be correlated with DAS28, ESR, CRP, white blood cell counts, neutrophil counts, and plasma TNF-α levels (r = 0.329, p = 0.005; r = 0.241, p = 0.043; r = 0.314, p < 0.001; r = 0.261, p = 0.028; r = 0.278, p = 0.019; and r = 0.313, p = 0.009, respectively). Plasma sTREM-1 levels in patients with active disease status (DAS28 > 3.2) were significantly higher than in those with low disease status (DAS28 ≤ 3.2; 208.89 ± 100.14 pg/ml vs 150.29 ± 68.70 pg/ml; p = 0.005).Conclusion.Patients with RA had higher plasma sTREM-1 levels than healthy controls, and plasma sTREM-1 levels were correlated with disease activity measures, suggesting that plasma sTREM-1 could play a role in the inflammatory process associated with TNF-α, and that it may be a useful disease activity marker in RA.

scholarly journals Antcin K Inhibits TNF-α, IL-1β and IL-8 Expression in Synovial Fibroblasts and Ameliorates Cartilage Degradation: Implications for the Treatment of Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
David Achudhan ◽  
Shan-Chi Liu ◽  
Yen-You Lin ◽  
Chien-Chung Huang ◽  
Chun-Hao Tsai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cytokine Production ◽  
Bone Erosion ◽  
Interleukin 1 ◽  
Synovial Fibroblasts ◽  
Nuclear Factor Κb ◽  
Cartilage Degradation ◽  
Signaling Cascades ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Extracts from Taiwan’s traditional medicinal mushroom, Antrodia cinnamomea, exhibit anti-inflammatory activities in cellular and preclinical studies. However, this paper is the first to report that Antcin K, a triterpenoid isolated from A. cinnamomea, inhibits proinflammatory cytokine production in human rheumatoid synovial fibroblasts (RASFs), which are major players in rheumatoid arthritis (RA) disease. In our analysis of the mechanism of action, Antcin K inhibited the expression of three cytokines (tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β] and IL-8) in human RASFs; cytokines that are crucial to RA synovial inflammation. Notably, incubation of RASFs with Antcin K reduced the phosphorylation of the focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and nuclear factor-κB (NF-κB) signaling cascades, all of which promote cytokine production in RA. Intraperitoneal injections of Antcin K (10 mg/kg or 30 mg/kg) attenuated paw swelling, cartilage degradation and bone erosion, and decreased serum levels of TNF-α, IL-1β, IL-8 in collagen-induced arthritis (CIA) mice; in further experiments, IL-6 levels were similarly reduced. The inhibitory effects of Antcin K upon TNF-α, IL-1β and IL-8 expression in human RASFs was achieved through the downregulation of the FAK, PI3K, AKT and NF-κB signaling cascades. Our data support clinical investigations using Antcin K in RA disease.

scholarly journals Correlation of level of expression of Wnt Signaling Pathway Inhibitor Dickkopf-1 with disease activity in Elderly patients of Rheumatoid Arthritis: A cross sectional study

2019 ◽  
Vol 9 (1) ◽  
pp. 348-350
Author(s):  
ANUP SINGH
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Bone Erosion ◽  
Wnt Signaling Pathway ◽  
Cross Sectional Study ◽  
Age Group ◽  
Serum Samples ◽  
Elderly Age ◽  
Cross Sectional ◽  
Dickkopf 1

Objective: To correlate the level of Dickkopf-1 (DKK-1) and its role in rheumatoid arthritis (RA) patients of elderly age group. Methods:  Serum samples were collected elderly RA patients fulfilling the inclusion criteria coming to Geriatric outdoor clinic between June 2018 to September 2018. DKK-1 was detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA. Results: Twenty one patients were enrolled in study period. The serum level of DKK-1 was significantly higher in patients with severe RA with high DAS score (p < 0.01); The serum DKK-1 level was correlated with T-score (r= -0.588; p = 0.005), Z-Score(r= -0.458, p = 0.037) and the larson score of radiologic change (r = +0.673, p = 0.001) in RA, however not correlated significantly with ESR, CRP. Conclusion: DKK-1 may serve as a biomarker of bone erosion and correlates with the disease activity in RA patients of elderly age group. Keyword: DKK 1, Rheumatoid arthritis, Geriatric, Osteoporosis.

Circulating Dickkopf-1 and Radiological Progression in Patients with Early Rheumatoid Arthritis Treated with Etanercept

2008 ◽  
Vol 35 (12) ◽  
pp. 2313-2315 ◽  
Author(s):  
PATRICK GARNERO ◽  
NADINE CHARNI-BEN TABASSI ◽  
NATHALIE VOORZANGER-ROUSSELOT
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
C Reactive Protein ◽  
Radiological Progression ◽  
Reactive Protein ◽  
Important Mediator ◽  
Risk Of Progression ◽  
Radiological Damage ◽  
Dickkopf 1

ObjectiveDickkopf-1 (Dkk-1) regulates bone remodeling in animal models of inflammatory arthritis, but its role in patients with rheumatoid arthritis (RA) remains unclear.MethodsBaseline circulating Dkk-1 was measured in 113 patients with RA (< 3 yrs) who received etanercept (10 or 25 mg twice/week, n = 63) or methotrexate alone (n = 40) for 1 year. Progression was assessed by changes in radiological Sharp score.ResultsIncreased Dkk-1 was associated with a higher risk of progression of bone erosion, independently of age, sex, baseline radiological damage, C-reactive protein, and disease activity in patients treated with etanercept.ConclusionDkk-1 may be an important mediator of bone erosion in patients with RA.

Differences in MSU-induced Superoxide Responses by Neutrophils from Gout Subjects Compared to Healthy Controls and a Role for Environmental Inflammatory Cytokines and Hyperuricemia in Neutrophil Function and Survival

2010 ◽  
Vol 37 (6) ◽  
pp. 1228-1235 ◽  
Author(s):  
WILLIAM JOHN MARTIN ◽  
REBECCA GRAINGER ◽  
ANDREW HARRISON ◽  
JACQUIE L. HARPER
Keyword(s):  
Neutralizing Antibodies ◽  
Ex Vivo ◽  
Elevated Serum ◽  
Neutrophil Function ◽  
Superoxide Production ◽  
Healthy Controls ◽  
Serum Samples ◽  
Tnf Α ◽  
Neutrophil Superoxide ◽  
Factor Α

Objective.To determine whether monosodium urate (MSU) crystal-induced superoxide production is greater for neutrophils from patients with gout compared to asymptomatic hyperuricemic and healthy controls, and whether neutrophil functions are altered by an MSU crystal-induced inflammatory environment.Methods.Neutrophils were purified from the whole blood of study participants, restimulated with 500 mg MSU crystalsex vivo, and superoxide production measured using the colorimetric dye WST-1. Purified neutrophils were exposed to conditioned media from MSU crystal-activated blood monocyte cultures with and without neutralizing antibodies for interleukin 1ß (IL-1ß), IL-8 (CXCL8), IL-6, and tumor necrosis factor-α (TNF-α). Neutrophil superoxide production was measured and neutrophil apoptosis and IL-8 production were determined by flow cytometry. Serum samples were collected from participants and analyzed by Lincoplex bead array for IL-1ß, IL-8, IL-6, and TNF-α.Results.Neutrophils from gout and asymptomatic hyperuricemic subjects produced higher levels of MSU crystal-induced superoxide, and a weak trend toward elevated serum cytokines was observed compared to healthy controls. A correlation between serum uric acid and elevated neutrophil superoxide production was also observed. Neutrophils exposed to media from MSU crystal-activated monocytes exhibited enhanced superoxide production to MSU-crystal stimulation, increased IL-8 production, and extended cell survival that was predominantly dependent on IL-8, TNF-α and IL-6, respectively.Conclusion.Neutrophils from gout and asymptomatic hyperuricemic individuals are primed for enhanced MSU crystal-induced superoxide production that may be driven by a subclinical inflammatory cytokine environment combined with hyperuricemia. This inflammatory environment likely contributes to elevated neutrophil IL-8 production and survival in the absence of direct crystal stimulation. Asymptomatic hyperuricemia is not associated with suppressed neutrophil function.

scholarly journals POS0346 THE THERAPEUTIC EFFECTS OF OMEGA-6 PUFA (PINOLENIC ACID) ON THE TRANSCRIPTOMIC PROFILE OF ACTIVATED PERIPHERAL BLOOD MONONUCLEAR CELLS ISOLATED FROM HEALTHY CONTROLS AND RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 402-403
Author(s):  
R. Takala ◽  
D. Ramji ◽  
R. Andrews ◽  
Y. Zhou ◽  
J. Burston ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Pathway Analysis ◽  
Healthy Controls ◽  
Pinolenic Acid ◽  
Eular Recommendations ◽  
Tnf Α ◽  
Omega 6 ◽  
Disease Modifying ◽  
Anti Inflammatory

Background:Globally, Rheumatoid arthritis (RA) is the most common chronic inflammatory arthritis. EULAR recommends patient education and disease modifying anti-rheumatic drugs including advanced targeted therapies for management1 2. Many patients seek advice on a dietary intervention that may improve symptoms. Foods high in omega-3 polyunsaturated fatty acids (PUFAs) is one of the most common recommended based on their anti-inflammatory properties3 4. Previously we showed pinolenic acid (PNLA), an omega-6 (PUFAs) found in pine nuts, reduced lipid uptake, endocytosis and migration of monocyte in vitro. PNLA also reduced IL-6, TNF-α, IL-1β and PGE2 produced by lipopolysaccharide (LPS) activated PBMCs from patients with RA and healthy controls (HCs).Objectives:We hypothesis that PNLA inhibits key inflammatory processes in synovities as in diagram.1. We investigated the transcriptomic profile of PNLA treatment on LPS activated PBMCs isolated from HCs and RA patients.Methods:Adult RA patients (n=6) were recruited from the Rheumatology Department of University Hospital of Wales together with 6 HCs. Blood was collected after taking signed informed consent. PBMCs were isolated by Ficoll gradient centrifugation and pre-treated with 25 μM PNLA or vehicle and then activated with 100 ng/ml LPS. RNA was extracted followed by library construction and sequencing for whole genomic transcriptome. DEGs were analysed using DESeq2 and pathway analysis was performed using Ingenuity pathway analysis. The study was approved by the Research Ethics Committee for Wales (reference no. 12/WA/0045).Results:DEGs were selected with at least differential genes using at least 1.2* fold changes and adjusted p-value of <0.05. PNLA significantly upregulates the expression of PDK4, PAI-1 (SERPINE1), FBP1, and NDRG2. These genes have important roles in metabolic pathways. Pathway analysis predicted upstream activation of nuclear receptors peroxisome proliferator-activated receptor (PPARs) involved in the anti-inflammatory process, and inhibition of NF-κB and STAT1, the major transcription factors of the pro-inflammatory cytokines TNF-α, IL-1, IL-6 and IFN-γ.Conclusion:PNLA has significant effects on the regulation of metabolic and inflammatory pathways in PBMCs from RA patients and HCs. Based on these results we demonstrate that PNLA may have beneficial anti-inflammatory effects in patients with RAReferences:[1]Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes. IB, Peters MJL, Kvien, TK., Dougados, M, Radner, H, Atzeni, F. and Primdahl, J. 2017. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Annals of the rheumatic diseases, 76(1), pp.17-28.[2]Smolen JS, Landewé RBM, Bijlsma JWJ, et al. 2019. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: updateAnnals of the Rheumatic Diseases 2020; 79:685-699.[3]Chehade L, Jaafar ZA, El Masri D, Zmerly H, Kreidieh D, Tannir H, Itani L, and El Ghoch, M. 2019. Lifestyle Modification in Rheumatoid Arthritis: Dietary and Physical Activity Recommendations Based on Evidence. Current rheumatology reviews, 15(3), pp.209-214.[4]Marchand NE, Chiu Y-H, Yoshida K, Malspeis S, Sparks JA, Costenbader K, et al. Threshold Level for Long-term Healthy Diet Adherence to Reduce the Risk of Rheumatoid Arthritis Among Women in a Prospective Cohort Using a Marginal Structural Model Approach.:25.Diagram 1.Disclosure of Interests:None declared

scholarly journals Interleukin-37 as an anti-inflammatory cytokine: does its relation to disease activity suggest its potential role in rheumatoid arthritis therapy?

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Eman A. Baraka ◽  
Mona G. Balata ◽  
Shereen H. Ahmed ◽  
Afaf F. Khamis ◽  
Enas A. Elattar
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Tender Joint ◽  
Cross Sectional ◽  
Reactive Protein ◽  
Significant Difference ◽  
The Mean ◽  
Anti Inflammatory

Abstract Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.

scholarly journals THU0105 ISOTOPE-LABELING-LC-MS-BASED METABOLIC PROFILING OF MULTIPLE SERUM SAMPLE SETS FOR THE DISCOVERY OF HIGH-CONFIDENCE RHEUMATOID ARTHRITIS BIOMARKERS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 266.2-267
Author(s):  
W. Han ◽  
X. Wang ◽  
L. Li ◽  
S. Wichuk ◽  
E. Hutchings ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Performance ◽  
Isotope Labeling ◽  
Support Vector ◽  
Healthy Controls ◽  
High Confidence ◽  
Serum Samples ◽  
Worst Case ◽  
Advisory Boards ◽  
Pooled Sample

Background:Early diagnosis of rheumatoid arthritis (RA) is hampered by suboptimal accuracy of currently available serological biomarkers. Metabolomics may reveal promising biomarker candidates associated with the biomolecular processes of RA. In this work, we applied a high-performance chemical isotope labeling (CIL) LC-MS technique for in-depth profiling of the amine/phenol-submetabolome in serum samples. To avoid false positives and obtain high-confidence biomarker candidates, we analyzed three independent sets of serum samples collected from RA patients and healthy controls to examine the common effects.Objectives:We aimed to identify a metabolite signature with consistently high accuracy for RA.Methods:Serum samples were taken from 3 RA cohorts, which comprised 50, 49, and 131 RA patients, respectively. Within each cohort, there were sex/age-matched healthy controls: 50 in Cohort 1, 50 in Cohort 2, and 100 in Cohort 3. Among these 446 subjects, 75% were females and the average age was 52.5 years. Amine/phenol-containing metabolites were labeled by12C-dansyl chloride to improve the LC-MS detection. For each cohort, a pooled sample was prepared and labeled by13C-dansyl group to serve as the reference sample for relative quantification. Then the individual samples and the pooled sample were mixed 1:1. Finally, an LC-QTOF-MS platform analyzed the mixtures and output the intensity ratios of12C/13C peak pairs.Results:1,149 amine/phenol-containing metabolites were commonly detected across the three sample sets. Among them, 134 were positively identified by our dansyl-labeling standard library, and 141 were matched to predicted retention times and mass values of dansyl-labeled human metabolites. Visualized by the partial least squares discriminant analysis (PLS-DA), the overall amine/phenol-submetabolome demonstrated clear and consistent differences between healthy controls and the RA groups, with cross-validation Q2 = 0.765, 0.745, 0.793, respectively. The selection of significant metabolites was conducted according to the fold change and false-discovery-rate-adjusted Welch’s t-test. Cohort 1 demonstrated 85 metabolites having higher concentrations in the RA samples than the controls, and 89 metabolites with lowered concentrations. The numbers of increased/decreased metabolites in Cohort 2 and 3 were 87/26 and 90/53, respectively. Importantly, there were 59 significantly discriminatory metabolites commonly found in the three data sets (49 increased and 9 decreased). We picked the top three with the highest univariate classification performance to form a biomarker panel. We implemented the linear support vector machine (SVM) to build the classifier and the receiver operating characteristic (ROC) analysis to measure the performance. The area-under-the-curve (AUC) values (95% confidence interval) were 1.000 (1.000-1.000), 0.992 (0.967-1.000) and 0.902 (0.858-0.945) for the three cohorts, respectively. The results revealed the importance of examining multiple sample sets and even in the worst case (Cohort 3), our biomarker candidates could differentiate RA at 82.5% sensitivity and 82.5% specificity. Particularly, in Cohort 3, there were 30 RA patients negative for anti-cyclic citrullinated peptide and rheumatoid factor, and our metabolite panel demonstrated consistently high performance for differentiating these specific subjects from healthy controls.Conclusion:Metabolites showing significant and consistent changes associated with RA have been identified with high discriminative power.Disclosure of Interests:Wei Han: None declared, Xiaohang Wang: None declared, Liang Li: None declared, Stephanie Wichuk: None declared, Edna Hutchings: None declared, Rana Dadashova: None declared, Joel Paschke: None declared, Walter P Maksymowych Grant/research support from: Received research and/or educational grants from Abbvie, Novartis, Pfizer, UCB, Consultant of: WPM is Chief Medical Officer of CARE Arthritis Limited, has received consultant/participated in advisory boards for Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Received speaker fees from Abbvie, Janssen, Novartis, Pfizer, UCB.

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