scholarly journals Adipocytokines in Untreated Newly Diagnosed Rheumatoid Arthritis: Association with Circulating Chemokines and Markers of Inflammation

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 325
Author(s):  
Georgios K. Vasileiadis ◽  
Anna-Carin Lundell ◽  
Yuan Zhang ◽  
Kerstin Andersson ◽  
Inger Gjertsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Positive Association ◽  
Enzyme Linked Immunosorbent Assay ◽  
Newly Diagnosed ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Hmw Adiponectin ◽  
Total Adiponectin ◽  
Inflammatory Chemokines

Adiponectin, leptin, and resistin are adipocytokines whose levels are elevated in blood and synovial fluid from patients with rheumatoid arthritis (RA). However, their role in RA pathogenesis is unclear. Here, we examined whether adipocytokines are associated with circulating chemokines, markers of inflammation and RA disease activity in patients with untreated newly diagnosed RA. Plasma levels of 15 chemokines, adiponectin, leptin, and resistin were measured using flow cytometry bead-based immunoassay or enzyme-linked immunosorbent assay (ELISA) in a cohort of 70 patients with untreated newly diagnosed RA. Markers of inflammation and disease activity were also assessed in all patients. Positive association was found between total adiponectin and CXCL10 (β = 0.344, p = 0.021), CCL2 (β = 0.342, p = 0.012), and CXCL9 (β = 0.308, p = 0.044), whereas high-molecular weight (HMW) adiponectin associated only with CXCL9 (β = 0.308, p = 0.033). Furthermore, both total and HMW adiponectin were associated with C-reactive protein (β = 0.485, p = 0.001; β = 0.463, p = 0.001) and erythrocyte sedimentation rate (β = 0.442, p = 0.001; β = 0.507, p < 0.001). Leptin and resistin were not associated with plasma chemokines, markers of inflammation, or disease activity scores. Our study shows an association between circulating adiponectin and pro-inflammatory chemokines involved in RA pathogenesis as well as markers of inflammation in a well-characterized cohort of patients with untreated newly diagnosed RA.

Total and high-molecular weight plasma adiponectin associates with markers of inflammation and circulating chemokines in subjects with untreated newly diagnosed rheumatoid arthritis.

2020 ◽  
Author(s):  
Georgios K. Vasileiadis ◽  
Anna-Carin Lundell ◽  
Yuan Zhang ◽  
Kerstin Andersson ◽  
Inger Gjertsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Weight ◽  
Disease Activity ◽  
High Molecular Weight ◽  
Plasma Levels ◽  
Metabolic Effects ◽  
Inflammatory Factor ◽  
Newly Diagnosed ◽  
Markers Of Inflammation ◽  
Hmw Adiponectin

Abstract Background Adiponectin is an adipokine circulating in blood in three forms, whereof the high molecular weight (HMW) is supposed to mediate the metabolic effects of adiponectin. Subjects with rheumatoid arthritis (RA) have elevated levels of adiponectin in serum and synovial fluid but it is unclear if circulating adiponectin associates with disease activity markers in subjects with RA. Here we aimed to determine whether total and/or HMW adiponectin levels associate with markers of disease activity and plasma chemokines in a cohort of subjects with untreated newly diagnosed RA.Methods Inflammation and disease activity were assessed in a cohort of 70 subjects with untreated newly diagnosed RA using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), number of tender or swollen joints, as well as disease activity scores (DAS28 and CDAI) Plasma levels of 15 chemokines were measured using flow cytometry bead-based immunoassay or ELISA. Total and HMW adiponectin plasma levels were determined with ELISA.Results Both total and HMW adiponectin were positively associated with CRP (both P = 0.001) and ESR (P = 0.001 and P < 0.001 respectively). Furthermore, a positive association was found between total adiponectin and CXCL10 (P = 0.021), CCL2 (P = 0.012) and CXCL9 (P = 0.044), whereas HMW adiponectin associated with CXCL9 only (P = 0.033).Conclusion Total and HMW adiponectin are associated with markers of inflammation as well as pro-inflammatory chemokines in a cohort of 70 subjects with untreated newly diagnosed RA. Our results support the hypothesis that adiponectin might be a pro-inflammatory factor involved in the pathogenesis of RA.

Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab

2020 ◽  
Vol 79 (7) ◽  
pp. 874-882
Author(s):  
Inbal Haya Shafran ◽  
Farideh Alasti ◽  
Josef S Smolen ◽  
Daniel Aletaha
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Responses ◽  
Activity Index ◽  
Disease Activity Index ◽  
Positive Association ◽  
C Reactive Protein ◽  
Therapeutic Success ◽  
Reactive Protein ◽  
Early Ra

BackgroundRheumatoid arthritis (RA) is characterised by clinical joint swelling and elevation of acute phase reactant levels, typically measured by the C-reactive protein (CRP). Clinical and inflammatory responses are usually concordant, except for inhibition of IL-6, which often disproportionally reduces the CRP due to direct inhibition of its hepatic production. We investigated whether pre-treatment CRP is a useful marker that can guide a preferential treatment choice towards IL-6 inhibition.MethodsData of 1126 treatment courses with tocilizumab (TCZ; early RA), 250 courses of rituximab (RTX; established RA) and 249 courses of methotrexate (MTX; established RA) were analysed. We compared clinical disease activity index (CDAI) values and change along 24 weeks’ follow-up to CRP values at baseline or its early change. We validated the results using data from a separate TCZ trial in early RA.ResultsCRP levels in the TCZ group on average dropped by 74% within 4 weeks. Patients who attained CDAI remission at 24 weeks on TCZ had the highest baseline CRP levels while patients in high disease activity had the lowest; this association was reverse in the RTX and MTX groups. TCZ patients who achieved remission at 24 weeks showed the largest reductions of CRP levels by week 4 compared with those reaching higher disease activity states. Early CRP non-response was indicative of a risk of not achieving clinical treatment goals (p=0.038).ConclusionBaseline CRP appears to have a positive association with reaching the therapeutic target on TCZ treatment, but is a negative predictor for RTX and MTX. Patients on TCZ without an early CRP response have a lower chance of achieving remission. CRP and its early course may inform, to some extent, the estimation of potential therapeutic success in patients with RA.

scholarly journals Serum etanercept concentrations in relation to disease activity and treatment response assessed by ultrasound, biomarkers and clinical disease activity scores: results from a prospective observational study of patients with rheumatoid arthritis

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001985
Author(s):  
Johanna Elin Gehin ◽  
Silje Watterdal Syversen ◽  
David John Warren ◽  
Guro Løvik Goll ◽  
Joseph Sexton ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Observational Study ◽  
Disease Activity ◽  
Treatment Response ◽  
Therapeutic Range ◽  
Power Doppler ◽  
Therapeutic Drug ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Markers Of Inflammation

ObjectivesTo identify the therapeutic range for etanercept and to assess the incidence of anti-etanercept antibody formation.MethodsAssociations between etanercept serum concentration and disease activity as well as treatment response were examined in a longitudinal observational study of rheumatoid arthritis patients starting etanercept. Disease activity was assessed by ultrasound (grey scale and power Doppler), 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index, plasma calprotectin and C reactive protein. Etanercept concentration and anti-etanercept antibodies were analysed using automated in-house fluorescence assays.ResultsA total of 89 patients were included, whereof 66% were biological disease-modifying antirheumatic drug (DMARD) naïve and 91% used concomitant synthetic DMARD. At 3 months, the median etanercept concentration was 1.8 (IQR 1.1–2.5) mg/L. Longitudinal associations were found between etanercept concentration and disease activity assessed by plasma calprotectin, C reactive protein and DAS28, but not between etanercept concentration and improvement in disease activity by any of the parameters at 3, 6 or 12 months of treatment. Etanercept concentrations were not significantly different among patients who achieved response or remission, compared with non-response or non-remission. Hence, no therapeutic range could be identified. None of the patients developed anti-etanercept antibodies.ConclusionDespite the use of sensitive and objective markers of inflammation, a therapeutic range could not be identified for etanercept. Hence, this study suggests that proactive therapeutic drug monitoring is unlikely to benefit rheumatoid arthritis patients treated with etanercept, but a potential benefit in certain clinical situations cannot be excluded.

scholarly journals AB0352 ANTICARDIOLIPIN ANTIBODIES AND ACTIVITY OF GIANT CELL ARTERITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1201.1-1201
Author(s):  
A. Hočevar ◽  
R. Jese ◽  
J. Kramarič ◽  
S. Cucnik ◽  
M. Tomsic ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Laboratory ◽  
Solid Phase ◽  
Anticardiolipin Antibodies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Newly Diagnosed ◽  
Reactive Protein ◽  
Study Inclusion Criterion ◽  
Healthy Control

Background:Anticardiolipin antibodies (aCL) can be detected in newly diagnosed GCA as reactive antibodies to endothelial lesions. Their prognostic role, as a marker of disease activity, has not been extensively studied in GCA.Objectives:Our aim was to determine whether aCL IgG might represent laboratory marker of active GCA.Methods:We included patients with new clinical diagnosis of GCA supported by histology or imaging between September 2011 and July 2019, who completed at least a 48-week follow-up at our secondary/tertiary rheumatology center. Follow up visits with predetermined clinical and laboratory tests, including aCL IgG, were performed 12, 24, 48, and 96 weeks after diagnosis. GCA relapse was defined as worsening or new disease activity after initial remission. Other reasons for the disease-related symptoms, elevated inflammatory markers (C reactive protein or erythrocyte sedimentation rate) had to be excluded. aCL IgG were determined in the patients’ sera samples at baseline and at follow up visits, using an in-house solid phase enzyme-linked immunosorbent assay1. A value above the 99th percentile of the healthy control population was taken as significant.Results:During the observation period we identified 288 newly diagnosed GCA patients. Two hundred and twelve GCA patients (66.5% females, median (IQR) age 73.9 (67.0–78.7) years) fulfilled the study inclusion criterion, among them 145 patients completed the 96-week follow up visit. At baseline, 129/212 (60.8%) GCA patients had positive aCL IgG. During in total 781 follow up visits, we recorded 77 (9.9%) episodes of active/relapsing GCA (clinical, laboratory or combined in 4 (5.2%), 48 (62.3%), 25 (32.5%) episodes, respectively). aCL IgG were present at 155/781 (19.8%) measurements (at 24/77 episodes of relapsing/active and 131/573 episodes of quiescent GCA). The correlation between active/relapsing GCA and aCL IgG positivity was only weekly positive (r coefficient=0.094; p= 0.015).Conclusion:The role of aCL IgG as a biomarker for GCA activity seems to be rather limited.References:[1]Božič B, et al. Int Arch Allerg Immunol. 1997; 112:19-26. doi.org/ 10.1159/000237426Disclosure of Interests:None declared

scholarly journals AB0304 IMMUNOGENICITY OF BIOLOGIC DRUGS IN THE CLINICAL PRACTICE IN THE BULGARIAN POPULATION OF PATIENTS SUFFERING FROM RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1451.3-1451
Author(s):  
K. Kraev ◽  
M. Geneva-Popova ◽  
S. Popova
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Disease Activity ◽  
Clinical Response ◽  
Neutralizing Antibodies ◽  
Tnf Alpha ◽  
Drug Bioavailability ◽  
Drug Induced ◽  
Etanercept Treatment ◽  
Markers Of Inflammation

Background:Biological drugs are protein derivatives that, as such, are highly immunogenic. In recent years there have been many conflicting opinions about the role of drug immunogenicity in clinical practice.Objectives:To evaluate the drug immunogenicity of TNF-alpha blocking drugs (etanercept and adalimumab) used to treat patients with rheumatoid arthritis. To determine whether their presence can alter the effect of treatment and to evaluate their role in the clinical practice of rheumatologists.Methods:121 patients with rheumatoid arthritis, as well as 31 healthy controls, similar in sex and age, were examined. They were all monitored at 0, 6, 12 and 24 months from the start of TNF-alpha blocker treatment. Demographics, vital signs, markers of inflammation such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity indices were examined at each visit, respectively. Drug-induced neutralizing antibodies, as well as drug bioavailability in patients treated with adalimumab, were examined by ELISA.Results:Drug-induced neutralizing antibodies to adalimumab were detected in 11.57% of patients at 6 month, in 17.64% of patients at 12 month, and 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not detected at 6 months, at 7.77% at 12 months, at 9.63% of patients at 24 months. Of the adalimumab patients who were having drug-induced antibodies, 92.59% had low drug bioavailability, while the remaining 7.41% of patients showed normal drug bioavailability despite the presence of drug-induced neutralizing antibodies. In terms of worsening of the disease activity, a positive correlation was found with the presence of drug antibodies - Pearson Correlation = 0.701, p = 0.001. Patients with poor clinical response and available drug antibodies receiving adalimumab were slightly more than those treated with etanercept at 12 and 24 months but the difference is non-significant-U = 0.527, p> 0.05 and U = 0.623, p> 0.05, respectively.Conclusion:Presence of drug-induced neutralizing antibodies in patients treated with adalimumab and etanercept has been associated with poor clinical response and worsening of the patient’s condition. Testing of drug-induced neutralizing antibodies as well as the drug bioavailability of the drug used can be used as reliable biomarkers in clinical rheumatology.References:[1]Benucci M., F.Li Gobbi, M. Meacii et al., “Antidrug antibodies against TNF-blocking agents: correlations between disese activity, hypersensitivity reactions, and different classes of immunoglobulins”, Biologics and Targets and Therapy, 2015: 9 7 -2.[2]Chen D., Y. Chen, W. Tsai et al., “ Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis”, Ann Rheum Dis. 2015 Mar; 74 (3).[3]Kalden J. and H. Schulze-Koops, “ Immunogenicity and loss of response to TNF inhibitors: implications for rheumatoid arthritis treatment ”, Nature Reviews Rheumatology, 2017 volume 13, 707–718.[4]Wolf-Henning Boehnck, N. Brembilla, “ Immunogenicity of biological therapies: causes and consequences, ” Expert Review of Clinical Immunology, Vol 14, 2018, Issue 6, 513-523Disclosure 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.

FRI0126 POOR ADHERENCE TO METHOTREXATE IS ASSOCIATED WITH PERSISTENT DISEASE ACTIVITY DURING FOLLOW-UP FOR RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 644.1-645
Author(s):  
J. H. Kang ◽  
S. E. Choi ◽  
H. Xu ◽  
D. J. Park ◽  
S. S. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Outcome ◽  
Disease Activity ◽  
Reactive Protein ◽  
Rate Score ◽  
Tertiary Center ◽  
Proportion Of Days Covered ◽  
Euroqol 5D ◽  
Control Disease

Objectives:Although methotrexate (MTX) is the cornerstone therapy in patients with rheumatoid arthritis (RA), adherence to MTX in these patients is typically suboptimal. Thus, we investigated the proportion of RA patients who were adherent to MTX and whether non-adherence to MTX affected the clinical outcome in these patients during follow-up.Methods:We enrolled 331 RA patients from a single tertiary center. Data were collected at the time of enrollment and then annually for 4 consecutive years. Adherence was defined by the proportion of days covered at 1 year. Patients were divided into two groups: patients who took more than 80% of MTX and those who did not. Univariate and multivariate analyses were performed to identify the association between drug compliance and clinical outcome.Results:Of the 331 RA patients, 8.7% had taken less than 80% of MTX during the follow-up period. Non-adherent patients had lower EuroQol-5D scores (P=0.013) and higher RAPID3 scores (P=0.004) at baseline than adherent patients. Leflunomide was more commonly prescribed to adherent patients than non-adherent patients (P=0.012). Non-adherent patients had a higher mean Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate score (P=0.001), higher mean DAS28-C-reactive protein (CRP) score (P=0.001), and higher mean rate of tender and swollen joints (P=0.003 and P=0.002, respectively) than adherent patients. In the multivariate analysis, poor MTX adherence was significantly associated with a higher mean DAS28-CRP score (odds ratio, 0.270; 95% confidence interval, 0.165–0.444; P<0.001).Conclusion:Adherence to MTX can affect disease activity during follow-up in Korean patients with RA. Our results provide a rationale for patient education to maintain good drug adherence in RA patients, to control disease activity.Disclosure of Interests:None declared

scholarly journals Effects of Antitumor Necrosis Factor Therapy on Osteoprotegerin, Neopterin, and sRANKL Concentrations in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Kurz ◽  
Manfred Herold ◽  
Elisabeth Russe ◽  
Werner Klotz ◽  
Guenter Weiss ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Systemic Autoimmune Disease ◽  
Das28 Score ◽  
Reactive Protein ◽  
Adalimumab Therapy ◽  
Receptor Activator ◽  
Joint Erosions ◽  
Factor Therapy ◽  
Necrosis Factor

Background. Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation.Methods. 20 female patients with moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs.Results. Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin (rs=0.494,p=0.027), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (bothp<0.02). Patients who achieved remission (n=7) or showed a good response according to EULAR criteria (n=13) presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment (p=0.018for remission,p=0.011for good response).Conclusions. Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades.

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