scholarly journals Could potentially calprotectin be a promising biomarker to oracle biologic therapy response in rheumatoid arthritis?

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Rania Abd El-Hamid El-Kady ◽  
Ayah Fathy ◽  
Talaat Othman ◽  
Eman Hafez
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Biological Therapy ◽  
Biologic Therapy ◽  
S100 Protein ◽  
Therapy Response ◽  
Baseline Serum ◽  
Calprotectin Level ◽  
Remarkable Reduction

Abstract Background The advent of novel biologic agents for the treatment of rheumatoid arthritis (RA) has proven to be highly productive. Nonetheless, high cost, side effects, and unresponsiveness to these agents dictates the assignment of biomarkers that can foretell treatment response. Currently, calprotectin (a member of the S100 protein family) is amongst the enormously studied candidates in this perspective. Yet, conflicting results have been published. The main purpose of this study was to explore the role of serum concentration of calprotectin to predict the response to biological therapy in RA patients, so as to customize RA treatment. Results Baseline serum calprotectin levels were significantly higher in RA patients compared to the control subjects (P value < 0.001). After receiving biologic therapy, a remarkable reduction (P < 0.001) in serum calprotectin was noted in RA cohort. Moreover, no correlation was found between the 28 joint count disease activity score (DAS28) and serum calprotectin levels neither before or after biologics. Intriguingly, no statistically significant association was detected between circulating calprotectin level and response to biological therapy. Conclusion Serum calprotectin concentrations could not be used as a biomarker to forecast clinical response to biological therapy in RA patients. However, further studies involving larger cohort of RA patients should be carried out to deliver more insight in this regard.

scholarly journals FRI0596 NOVEL AUTOANTIBODY BIOMARKERS FOR THE PREDICTION OF THERAPY RESPONSE IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 904.1-904
Author(s):  
P. Vandormael ◽  
A. Pues ◽  
E. Sleurs ◽  
P. Verschueren ◽  
V. Somers
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapy Response ◽  
Autoimmune Disorder ◽  
First Line ◽  
Research Support ◽  
Serum Samples ◽  
Glucocorticoid Treatment ◽  
Baseline Serum ◽  
Disease Remission ◽  
Antibody Reactivity

Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each treatment will only induce disease remission in a subset of patients. Moreover, finding out which patients respond well to first-line therapy with classical synthetic disease modifying anti-rheumatic drugs (csDMARDs), still largely depends on trial and error.Objectives:In this study, we aim to find novel RA autoantibody biomarkers that predict therapy response to csDMARDs before the initiation of treatment.Methods:In the CareRA trial, a Flemish multicenter study of different treatment regimes, serum samples were collected from RA patients that did or did not show disease remission (DAS28(CRP)<2.6) in response to csDMARDs, combined with a step down glucocorticoid treatment. In our study, baseline samples, collected before the start of treatment, were used to determine predictive antibody reactivity. A cDNA phage display library, representing the antigens from RA synovial tissue, was constructed and screened for antibody reactivity in baseline serum samples of RA patients that failed to reach remission at week 16. Using enzyme-linked immunosorbent assays (ELISA), antibody reactivity against the identified antigens was initially determined in pooled baseline serum samples of RA patients that did (n=50) or did not (n=40) reach disease remission at week 16. Antigenic targets that showed increased antibody reactivity in pools from patients that did not reach disease remission, were further validated in individual serum samples of 69 RA patients that did not reach DAS28(CRP) remission at week 16, and 122 RA patients that did.Results:Screening and validation of antibody reactivity resulted in 41 novel antigens. The retrieved antigenic sequences correspond to (parts of) known proteins and to randomly formed peptides. A panel of 3 of these peptide antigens could be composed, whose baseline antibody reactivity correlated with lack of therapy response at week 16. Presence of antibodies against at least one of these 3 antigens was significantly higher in individual samples of RA patients that did not reach DAS28(CRP) remission (43 vs. 29%, p=0.041), or that failed to reach ACR 70 (42 vs. 26%, p=0.029) response criteria at week 16, compared to RA patients that did reach these respective criteria. In addition, RA patients which were positive for this antibody panel at baseline, also showed less DAS(CRP) remission at week 4 and week 8.Conclusion:We have identified a set of 3 antibody biomarkers that can predict failure of early disease remission after first-line RA therapy, which might contribute to personalized medicine decisions.Disclosure of Interests:Patrick Vandormael: None declared, Astrid Pues: None declared, Ellen Sleurs: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies, Veerle Somers Grant/research support from: Research grant from Pfizer and BMS

scholarly journals Histamine index and clinical expression of rheumatoid arthritis activity

2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Joint Destruction ◽  
Clinical Expression ◽  
Histamine Concentration ◽  
Significant Difference ◽  
Rheumatoid Arthritis Activity

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.

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 Serum Dickkopf-1 as a potential prognostic marker in patients with rheumatoid arthritis

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Dina A. Ali ◽  
Doaa Mohamed Esmail ◽  
Haidy Ali Mohammed ◽  
Reham Lotfy Yonis ◽  
Radwa Mahmoud El-Sharaby
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Joint Destruction ◽  
Control Group ◽  
Joint Erosions ◽  
Low Levels ◽  
Future Therapy ◽  
Dickkopf 1 ◽  
Inhibitory Regulation

Abstract Background Rheumatoid arthritis (RA) is a disease of an autoimmune nature that involves all types of joints structures and manifested by chronic joints inflammations and thus their erosions and damage. Dickkopf-1 (DKK-1) is a molecule that has an inhibitory regulation of wingless/integrated genes (Wnt) pathway and has a major role in models of animals with arthritis or joint destruction. Increased DKK-1 levels are implicated in higher resorption of the bone in cases of rheumatoid arthritis and thus with higher probability for joint deformities, while low levels associated with formation of new bone by osteoblasts, we aimed to study the prognostic role of circulating Dickkopf-1 in rheumatoid arthritis. Results The present study revealed that the DKK-1 levels were significantly increased in RA patients in relation to the control group (P=0.001). We found a significant positive correlation between DKK-1 level and ESR (P=0.001), Disease Activity Score (DAS 28) (P=0.001), the disease duration (P=0.001), and the presence of bone erosions in plain X-ray of hands (P =0.001). Moreover, we revealed that, at cutoff value 2150, the DKK-1 in RA has 90% sensitivity and 85% specificity. Conclusions DKK-l serum level can be used as a potential prognostic biomarker for monitoring of joint erosions and destruction in RA patients. Furthermore, it could be a possible target molecule in the future therapy to control the process of joint destruction.

Circulating Leptin and Adiponectin Concentrations During Tumor Necrosis Factor Blockade in Patients with Active Rheumatoid Arthritis

2009 ◽  
Vol 36 (4) ◽  
pp. 724-730 ◽  
Author(s):  
CALIN POPA ◽  
MIHAI G. NETEA ◽  
JACQUELINE de GRAAF ◽  
FRANK H.J. van den HOOGEN ◽  
TIMOTHY R.D.J. RADSTAKE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Active Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Serum Levels ◽  
Plasma Leptin ◽  
Necrosis Factor

Objective.Adipocytokines, including leptin and adiponectin, may play an important role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of longterm therapeutic tumor necrosis factor (TNF) blockade on adipocytokine concentrations in patients with RA.Methods.We studied 58 RA patients starting anti-TNF therapy and 58 healthy controls matched for age, sex, and body mass index (BMI). Fasting blood samples were drawn at baseline, 2 weeks, and 6 months after the start of anti-TNF therapy and serum levels of leptin and adiponectin were measured.Results.Patients with RA had increased adiponectin (p < 0.001) and similar leptin concentrations compared with the controls. Leptin concentrations were significantly higher in patients with high BMI (p < 0.001) and correlated positively with BMI at all timepoints (r > 0.75). In contrast, serum adiponectin tended to be higher in lean RA patients and did not correlate with BMI at any timepoint. There were no clear correlations between serum concentrations of adipocytokines and disease activity (Disease Activity Score 28). Short or longterm TNF blockade alone had no influence on circulating leptin and adiponectin concentrations. Patients treated with anti-TNF and concomitant corticosteroids on a stable basis showed a significant decrease in adiponectin levels after 6 months of therapy (p < 0.025).Conclusion.In patients with RA, chronic inflammation and its suppression during anti-TNF therapy have limited influence on plasma leptin concentrations, while significantly decreasing circulating adiponectin levels. Our findings question the suggested key role of inflammatory markers in regulating adipocytokine patterns in RA.

CASE 173: ASSESSMENT OF BIOLOGIC THERAPY RESPONSE IN RHEUMATOID ARTHRITIS

2016 ◽  
pp. 245-245
Author(s):  
Munir Ghesani ◽  
Nasrin Ghesani ◽  
E DePuey ◽  
Amir Kashefi ◽  
Yi Zhang
Keyword(s):  
Rheumatoid Arthritis ◽  
Biologic Therapy ◽  
Therapy Response

AB0504 The Role of Corticosteroids in Rheumatoid Arthritis Patients Under Biologic Therapy

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 1067.1-1067
Author(s):  
P.S. Madureira ◽  
S. Pimenta ◽  
R. Vieira ◽  
R. Fonseca ◽  
D.R. Gonçalves ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Biologic Therapy

scholarly journals Wnt Signaling and Biological Therapy in Rheumatoid Arthritis and Spondyloarthritis

2019 ◽  
Vol 20 (22) ◽  
pp. 5552 ◽  
Author(s):  
Daniela Cici ◽  
Addolorata Corrado ◽  
Cinzia Rotondo ◽  
Francesco P. Cantatore
Keyword(s):  
Rheumatoid Arthritis ◽  
Wnt Signaling ◽  
Cellular Proliferation ◽  
Biological Therapy ◽  
Wnt Signaling Pathway ◽  
Tnf Α ◽  
Bone Complications ◽  
Necrosis Factor

The Wnt signaling pathway plays a key role in several biological processes, such as cellular proliferation and tissue regeneration, and its dysregulation is involved in the pathogenesis of many autoimmune diseases. Several evidences support its role especially in bone complications of rheumatic diseases. In Rheumatoid Arthritis (RA), the Wnt signaling is implicated in systemic and localized bone loss, while available data of its role in Spondyloarthritis (SpA) are conflicting. In the last few decades, the quality of life of rheumatic patients has been dramatically improved by biological therapy, targeting cytokines involved in the pathogenesis of these diseases like tumor necrosis factor (TNF)α, interleukin (IL)-1, IL-6, IL-17. In this review, we reviewed the role of Wnt signaling in RA and SpA, focusing on the effect of biological therapy on this pathway and its possible clinical implications.

Etanercept Concentration in Patients with Rheumatoid Arthritis and Its Potential Influence on Treatment Decisions: A Pilot Study

2012 ◽  
Vol 39 (8) ◽  
pp. 1533-1538 ◽  
Author(s):  
CLAIRE IMMEDIATO DAÏEN ◽  
VINCENT DAÏEN ◽  
ERMIS PARUSSINI ◽  
ANNE-MARIE DUPUY ◽  
BERNARD COMBE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Therapy Response ◽  
Serum Concentrations ◽  
Potential Influence ◽  
Blocker Therapy ◽  
European League Against Rheumatism ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.For patients with rheumatoid arthritis (RA), recommendations are inconclusive about whether tumor necrosis factor-α (TNF-α)-blocker therapy should be evaluated at 3 or 6 months. Biomarkers are needed to predict at 3 months which patients would benefit from further treatment because of nonoptimal response. Our objective was to investigate whether serum etanercept (ETN) concentrations and anti-ETN antibodies at 3 months are predictors of clinical response to ETN at 6 months in patients with RA in terms of European League Against Rheumatism criteria and Disease Activity Score in 28 joints (DAS28).Methods.Between 2009 and 2010, we included 19 women with active RA who were candidates for ETN therapy. Response criteria were evaluated at 3 and 6 months. Serum concentrations of ETN and anti-ETN antibodies were measured by ELISA at baseline and at 3 and 6 months.Results.Eighteen patients completed followup. Three-month ETN concentrations were lower for 6-month nonresponders than responders (p = 0.03). Three-month ETN levels correlated significantly with change in DAS28 between baseline and 6 months (r = −0.62, p = 0.006). The best predictor of response at 6 months was observed with an ETN threshold of 3.1 μg/ml at 3 months. No anti-ETN antibodies were found.Conclusion.ETN concentrations at 3 months predict response to ETN therapy at 6 months. Low ETN concentrations could explain the absence of response to ETN, suggesting that patients with low ETN levels could benefit from increased ETN dose or earlier interruption of treatment.

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