scholarly journals Levels of CXCL13 and sICAM-1 correlate with disease activity score in patients with rheumatoid arthritis treated with tocilizumab

2019 ◽  
Vol 59 (1) ◽  
Author(s):  
Katie Tuckwell ◽  
Cem Gabay ◽  
Thierry Sornasse ◽  
Ruediger Paul Laubender ◽  
Jianmei Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Serum Levels ◽  
Activity Score ◽  
Intercellular Adhesion Molecule ◽  
Inadequate Response ◽  
Intercellular Adhesion Molecule 1 ◽  
Baseline Serum ◽  
Early Ra

Abstract Background Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA. Objectives To evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). Methods Baseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined. Results Overall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response. Conclusions Although CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.

scholarly journals AB0179 INFLUENCE OF AINFLUENCE OF ANTI-CITRULLINATED PROTEIN/PEPTIDE ANTIBODIES (ACPAS)ON ARTICULAR MANIFESTATIONS, DISEASE ACTIVITY AND STRUCTURAL SEVERITY IN ALGERIAN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1115.1-1115
Author(s):  
F. Rahal ◽  
N. Brahumi ◽  
A. Ladjouze-Rezig ◽  
S. Lefkir
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Activity Score ◽  
Symptom Duration ◽  
Early Ra ◽  
The Mean ◽  
Citrullinated Protein ◽  
Peptide Antibodies

Background:Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). There are also suggested to have a more severe rheumatoid arthritis.Objectives:The aim of this study was to assess the influence of ACPA on disease activity, radiological severity, and functional disability in Algerian patient with early rheumatoid arthritis (RA).Methods:Consecutive early RA patients (symptom duration ≤24 months) recruited were included in the descriptive, longitudinal, prospective study. Demographic, biological, immunological and radiographic data were collected at the time of inclusion in the study. Disease activity as determined by the Disease Activity Score 28-CPR (DAS28- CPR: 4 variables), functional handicap as calculated by Heath Assessment Score (HAQ), and bone and joint damage as evaluated by Sharp-Van der Heijde (SVDH) erosion and narrowing score.Results:One hundred and sixty-one patients with RA were recruited. Patients mean age 43.71±14 years and mean symptom duration at inclusion was 10.48±7 months. Small and larges were affected in 64,3%. The mean ESR was 23,53±15,2 mm/1st hour, and the mean CRP level was 19,42±39.8 mg/l. Rheumatoid Factors (RFs) and Anti-Citrullinated Protein Antibodies (ACPAs) were present in 74% and 88% of patients, respectively. The presence of ACPAs was significantly associated with DAS28 (p=0,004) and HAQ (p=0,002). There was no significant difference in inflammatory markers and radiographic SVDH score between patients with and without ACPAs. Stepwise regression analysis showed that the presence of ACPAs was independently associated with localization when RA affected smalls and larges joint in the same time (OR=5,24; IC 95% 1,224-22,483; p=0,026).Conclusion:These data show that in patients with early RA, ACPAs positivity was significantly associated with articular manifestations, activity disease and functional handicap, but not with structural damage.References:[1]Nikiphorou E, Norton S, Young A, et al. Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds. Ann Rheum Dis. 2016;75(12):2080-2086. doi:10.1136/annrheumdis-2015-208669.[2]Karimifar M, Salesi M, Farajzadegan Z. The association of anti-CCP1 antibodies with disease activity score 28 (DAS-28) in rheumatoid arthritis. Adv Biomed Res. 2012;1:30. doi:10.4103/2277-9175.98156.[3]Boman A, Brink M, Lundquist A, et al. Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study. RMD Open. 2019;5(2):e000946. Published 2019 Sep 3. doi:10.1136/rmdopen-2019-000946.Disclosure of Interests:None declared

scholarly journals Potential applicability of cytokines as biomarkers of disease activity in rheumatoid arthritis: Enzyme-linked immunosorbent spot assay-based evaluation of TNF-α, IL-1β, IL-10 and IL-17A

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246111
Author(s):  
Keerthie Dissanayake ◽  
Chandrika Jayasinghe ◽  
Priyani Wanigasekara ◽  
Ajith Sominanda
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Elispot Assay ◽  
Disease Activity Score ◽  
Activity Index ◽  
Pivotal Role ◽  
Activity Score ◽  
Early Ra ◽  
Tnf Α ◽  
Potential Applicability

Biomarkers play a pivotal role in the management of rheumatoid arthritis (RA) by facilitating early diagnosis and ‘treat to the target.’ However, no gold standard biomarker has been identified for monitoring the disease activity in RA. Cytokines, a diverse group of small protein molecules secreted by peripheral blood mononuclear cells (PBMCs), play a pivotal role in pathogenesis and disease progression in RA. Research is currently underway to find out the applicability of cytokines as biomarkers in RA. This study aimed to quantify the PBMCs that secrete four types of cytokines; TNF-α, IL-1β, IL-10 and IL-17A in two cohorts of active RA patients (early RA patients and established RA patients), compared to healthy controls (HC), using the enzyme-linked immunosorbent spot (ELISPOT) assay, and to assess their association with measures of disease activity of RA. Patients were recruited from outpatient rheumatology clinics, and the disease activity was assessed using single and composite measures of disease activity. The cytokine expression was evaluated using freshly separated PBMCs from whole blood of RA patients using the ELISPOT assay. The number of PBMCs (counted as spot-forming cells (SFCs) per 105 PBMCs) that secreted the cytokine of interest were statistically significantly higher in early RA patients, compared to HC, for IL-17A (P<0.05). Such an increased number of SFCs was not observed in the established RA group, compared to controls, for any of the cytokines tested. The correlation analysis showed that IL-17A is having a moderate correlation (Spearman`s ρ, p <0.05) with five clinical measures of disease activity, including disease activity score 28 (DAS28). According to the multivariable linear regression models, IL17A was a good predictor of both the disease activity score 28 (DAS28) and clinical disease activity index (CDAI). In conclusion, IL-17A has potential applicability as a biomarker of disease activity of RA.

scholarly journals Serum levels of reactive oxygen metabolites at 12 weeks during tocilizumab therapy are predictive of 52 weeks-disease activity score-remission in patients with rheumatoid arthritis

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Arata Nakajima ◽  
Keiichiro Terayama ◽  
Masato Sonobe ◽  
Yasuchika Aoki ◽  
Hiroshi Takahashi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Index ◽  
Multivariate Logistic Regression Analysis ◽  
Reactive Oxygen ◽  
Serum Levels ◽  
Activity Score ◽  
Reactive Oxygen Metabolites ◽  
Oxygen Metabolites

Abstract Background To verify whether serum levels of reactive oxygen metabolites (ROM) are predictive of future clinical remission in patients with rheumatoid arthritis (RA) receiving tocilizumab (TCZ) therapy. Methods A total of 46 patients with RA receiving TCZ therapy were enrolled in this study. Patients were divided into remission and non-remission groups based on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) or clinical disease activity index (CDAI) at 52 weeks. Associations between serum levels of ROM, C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) at 4 and 12 weeks and the remission by DAS28-ESR and CDAI at 52 weeks were investigated. Results There were no significant differences in CRP and MMP-3 between DAS- or CDAI-remission and non-remission groups at 12 weeks. However, ROM in DAS-remission group were significantly lower than those in the non-remission group. For ROM, the area under the curve of the receiver operating characteristic curve was 0.735 and the cut-off value that distinguished DAS-remission group from non-remission group was 305.5 U. Carr (sensitivity: 70.0%, specificity: 72.2%). A multivariate logistic regression analysis revealed that ROM at 12 weeks was associated with DAS-remission at 52 weeks (odds ratio: 6.067, 95% confidence interval: 1.305–28.203). Conclusion Serum levels of ROM at 12 weeks during TCZ therapy may be predictive of DAS-remission at 52 weeks in patients with RA.

scholarly journals The Relationship of Cytokines IL-13 and IL-17 with Autoantibodies Profile in Early Rheumatoid Arthritis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Isabela Siloşi ◽  
Mihail Virgil Boldeanu ◽  
Manole Cojocaru ◽  
Viorel Biciuşcă ◽  
Vlad Pădureanu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
High Specificity ◽  
Serum Levels ◽  
Activity Score ◽  
Serum Concentrations ◽  
Serum Samples ◽  
And Control

Aims.In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA), the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity.Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters.Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity.Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP.

Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to Disease Activity Score-28

Autoimmunity ◽  
2009 ◽  
pp. 1-1
Author(s):  
Jose Miguel Sempere-Ortells ◽  
Vicente Perez-Garcia ◽  
Gema Marin-Alberca ◽  
Alejandra Peris-Pertusa ◽  
Jose Miguel Benito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Score

Evaluation of Toll-like Receptor 2 Gene Expression in Rheumatoid Arthritis and Correlation with the Disease Activity

2019 ◽  
Vol 13 (2) ◽  
pp. 140-148
Author(s):  
Mai Nasser ◽  
Noha M. Hazem ◽  
Amany Atwa ◽  
Amina Baiomy
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Mrna Expression ◽  
Disease Activity Score ◽  
Activity Score ◽  
Tlr2 Expression ◽  
Positive Correlation ◽  
Tlr2 Mrna

Background: Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematic disease. It affects joints and bones. The exact etiology of RA is still unclear. Varied genetic and environmental factors have been associated with the increased risk for RA. Overactivation of Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseases including RA. Objective: The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritis patients and investigate its correlation with the disease activity. Materials and Methods: This study included 60 patients and 20 healthy individuals. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/ European League Against Rheumatism criteria (ACR/EULAR). All included subjects did not have any joint disorders and /or autoimmune diseases. RA disease activity was determined by the disease activity score of 28 joints. Whole blood was collected from all participants. Total RNA extraction was done. TLR2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR). Results: TLR2 mRNA expression was found to be significantly higher in RA patients compared to healthy controls. Also, a strong positive correlation was found between TLR2 expression level and the disease activity score. A non significant positive correlation was found between TLR2 expression and serum Rheumatoid Factor (RF) level. Conclusion: TLR2 pathway may have an important role in RA pathogenesis and could be a new biomarker for diagnosis and monitoring disease activity.

Anti-carbamylated Protein Antibodies and Serum Level of 14-3-3 Protein for Early Detection of Rheumatoid Arthritis Patient in Correlation with Rheumatoid Factor, Anti-CCP Antibodies, Disease Activity and Joint Damage using High Frequency Musculoskeletal Ultrasound

2020 ◽  
Vol 7 (2) ◽  
pp. 141-153
Author(s):  
Sahar A. Ahmed ◽  
Enas M. Darwish ◽  
Walaa A. Attya ◽  
Mai Samir ◽  
Mennatallah Elsayed ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Rheumatoid Factor ◽  
Disease Activity Score ◽  
Joint Damage ◽  
Musculoskeletal Ultrasound ◽  
Activity Score ◽  
Das 28 ◽  
Significant Difference ◽  
Hands And Feet

Background: Rheumatoid arthritis (RA) is a common progressive chronic inflammatory autoimmune disease which affects mostly small joints, causing pain, swelling, deformity, and disability. Although progress has been made in exploring RA nature, still there is a lot to know about the disease pathogenesis, diagnosis, and treatment. Aim of the Work: To investigate the role of serum anti-carbamylated protein antibodies and 14-3-3η in the diagnosis of RA compared to rheumatoid factor (RF), anti-CCP antibodies, and highfrequency musculoskeletal ultrasound used to assess the disease activity and joint damage. Methods: Serum anti-carbamylated protein antibodies and 14-3-3η were measured using ELISA in 61 RA patients and 26 normal controls. RA Disease Activity Score (DAS 28), X-ray and musculoskeletal ultrasound (hands and feet), carotid ultrasound (Intima-Media Thickness IMT) were used in assessing the RA disease. Results: Anti-carbamylated protein antibodies were significantly elevated in RA patients 4.5 (4.1- 8.9 U⁄ml) compared to the control 3.2(1.9- 4.3 U⁄ml) (p< 0.001) but 14-3-3η showed no significant difference. There was a significant positive correlation between anti-carbamylated protein antibodies, 14-3-3η levels and disease activity score assessed by DAS 28, increased IMT measured by carotid duplex, total synovitis and total erosion score were assessed by musculoskeletal ultrasound. There was no correlation between RF and anti-CCP antibodies. Anti-carbamylated protein antibodies were found to have 66.7% sensitivity and 85.2% specificity in RA diagnosis, while 14- 3-3η had 51.9% sensitivity and 72.1% specificity. Conclusion: Anti-carbamylated protein antibodies and 14-3-3η have a high sensitivity and specificity in RA diagnosis and had a correlation with the disease activity and joint damage.

scholarly journals SAT0033 USING CHROMOSOME CONFORMATION FOR INSIGHT INTO PATHOGENESIS OF EARLY RHEUMATOID ARTHRITIS ENDOTYPES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 946.2-947
Author(s):  
C. Duncan ◽  
E. Hunter ◽  
C. Koutsothanasi ◽  
M. Salter ◽  
A. Akoulitchev ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Inadequate Response ◽  
Loss Of Function ◽  
Inception Cohort ◽  
Chromosome Conformation ◽  
Patient Response ◽  
Early Ra ◽  
Longitudinal Response

Background:Rheumatoid arthritis (RA) is a chronic autoimmune disease with substantial immunopathogenic heterogeneity. It is well established that early diagnosis and initiation of effective therapy is crucial to prevent loss of function. Previously, various RA treatment trajectories have been identified, however there are currently no clinically validated biomarkers that can identify these trajectories at the start of treatment. Evaluation of the structural epigenome has revealed that chromosome conformation signatures (CCS) offer great potential as binary, informative biomarkers, and have been previously shown to predict early RA patient response to Methotrexate with 90% sensitivity (1). These signatures can also reveal highly regulated areas of the genome, which may be underpinning disease endotypes.Objectives:The objective of this study was to evaluate the structural epigenome in early RA over longitudinal samples to determine whether it is associated with treatment trajectories.Methods:Patient data and samples were from the Scottish Early Rheumatoid Arthritis (SERA) cohort; a pan-Scotland inception cohort. CDAI, DAS28 ESR and DAS28 CRP measurements were calculated at baseline, 6 months and 12 months to determine longitudinal treatment response. From 3 principal longitudinal response trajectories, 18 patients (who had equivalent disease activity at baseline) were chosen to investigate the structural epigenome. These 18 comprised of responders (R), non-responders (NR) and initial responders (IR; low disease activity/remission at 6 months but moderate/high disease activity at 12 months) with 6 patients per group at each time point. 20 pooled healthy samples were used as a comparator population. EpiSwitch libraries were probed on 180K Agilent SureSelect custom arrays that were designed using EpiSwitch propriety information and publicly available data from Walshet al(2). Microarray data was analysed using the Limma package within R studio.Results:EpiSwitch array analysis showed that there were >10,000 statistically significant differential chromosomal loops between R, NR and IR. Evaluation of the 3 trajectory groups (R, NR and IR), taking into account the healthy chromosomal conformation, revealed an RA-associated structural epigenome that comprised of 10,445 chromosomal loops that were stable, over the three time points. Subsequent analysis of the distinct treatment trajectories demonstrated that 3683 of the stable, disease-associated chromosomal loops were shared by all 3. However, 4496 were associated with distinct response trajectories, with 1221, 2574 and 701 loops unique to R, NR and IR respectively.Conclusion:The stable chromosomal architecture unique to each treatment trajectory suggests that various underlying molecular endotypes may exist. Moreover, the stable loops common to all groups allude to a baseline level of dysregulation in RA and offers the potential to discover novel drivers of disease. This work provides the foundation to further our understanding of RA pathogenesis and the potential of finding a biomarker that would be of significant value in a clinical setting.References:[1] Carini, C., Hunter, E., Scottish Early Rheumatoid Arthritis Inception cohort Investigators, Ramadass, A. S., Green, J., Akoulitchev, A., et al. (2018). Chromosome conformation signatures define predictive markers of inadequate response to methotrexate in early rheumatoid arthritis.Journal of Translational Medicine,16(1), 18–11[2] Walsh, A. M., Whitaker, J. W., Huang, C. C., Cherkas, Y., Lamberth, S. L., Brodmerkel, C., et al. (2016). Integrative genomic deconvolution of rheumatoid arthritis GWAS loci into gene and cell type associations.Genome Biology,17(1), 2205Disclosure of Interests:Caitlin Duncan: None declared, Ewan Hunter: None declared, Christina Koutsothanasi: None declared, Matthew Salter: None declared, Alexandre Akoulitchev: None declared, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Carl Goodyear: None declared

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