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.

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.

scholarly journals Linoleic Acid–Rich Oil Supplementation Increases Total and High-Molecular-Weight Adiponectin and Alters Plasma Oxylipins in Postmenopausal Women with Metabolic Syndrome

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Rachel M Cole ◽  
Sarah Puchala ◽  
Jia-Yu Ke ◽  
Mahmoud Abdel-Rasoul ◽  
Kristin Harlow ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Molecular Weight ◽  
Linoleic Acid ◽  
High Molecular Weight ◽  
Oil Consumption ◽  
Open Label ◽  
High Molecular Weight Adiponectin ◽  
Markers Of Inflammation ◽  
Hmw Adiponectin ◽  
Total Adiponectin

ABSTRACT Background The onset of menopause increases the risk of metabolic syndrome (MetS). Adiponectin is an adipokine associated with insulin sensitivity that is lower in people with MetS. Supplementing diets with linoleic acid (LA)-rich oil increased adiponectin concentrations and improved glucose control in women with type 2 diabetes. The effect of LA on adipokines, especially total and the bioactive form of adiponectin, high-molecular-weight (HMW) adiponectin, in women with MetS is unknown. Objectives The aim of this study was to explore the effect of supplementation of the diet with an oil rich in LA on adipokines in women with MetS. The effect of the LA-rich oil (LA-oil) on oxylipins, key metabolites that may influence inflammation and metabolism, was also explored. Methods In this open-label single-arm pilot study, 18 postmenopausal nondiabetic women with MetS enrolled in a 2-phase study were instructed to consume LA-rich vegetable oil (10 mL/d) as part of their habitual diets. Women consumed an oleic acid–rich oil (OA-oil) for 4 wk followed by an LA-oil for 16 wk. Fasting concentrations of adipokines, fatty acids, oxylipins, and markers of glycemia and inflammation were measured. Results After 4 wk of OA-oil consumption, fasting glucose and total adiponectin concentrations decreased whereas fasting C-reactive protein increased. After 16 wk of LA-oil supplementation total and HMW adiponectin and plasma oxylipins increased. Markers of inflammation and glycemia were unchanged after LA-oil consumption. Conclusions Supplementation with LA-oil increased total and HMW adiponectin concentrations and altered plasma oxylipin profiles. Larger studies are needed to elucidate the links between these changes and MetS. This trial was registered at clinicaltrials.gov as NCT02063165.

scholarly journals Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Eric Toussirot ◽  
Hubert Marotte ◽  
Denis Mulleman ◽  
Grégoire Cormier ◽  
Fabienne Coury ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Weight ◽  
Body Composition ◽  
Multicentre Study ◽  
High Molecular Weight ◽  
Fat Mass ◽  
Lean Mass ◽  
Open Label ◽  
Hmw Adiponectin ◽  
Cv Disease

Abstract Background Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined. Methods Patients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months. Results One hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p < 0.0001), then declining progressively until month 6 to 12 and returning to baseline values. Significant elevation in HMW adiponectin persisted at month 6 (p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up. Conclusions Tocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle. Trial registration The ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).

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 Effects of Delayed Sample Processing on Determination of Total and High Molecular Weight (HMW) Adiponectin in Serum and Plasma: A Pilot Study

2016 ◽  
Vol 8 (3) ◽  
pp. 19
Author(s):  
Choaping Ng ◽  
Felicity J Rose ◽  
Sahar Keshvari ◽  
Marina M Reeves ◽  
Goce Dimeski ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pilot Study ◽  
High Molecular Weight ◽  
Accurate Determination ◽  
Mean Difference ◽  
Serum Samples ◽  
Blood Samples ◽  
Hmw Adiponectin ◽  
Total Adiponectin

<p>Adiponectin is a beneficial adipocyte-secreted hormone, which circulates in a variety of multimeric forms termed low and high molecular weight (LMW/HMW). Effectiveness of clinical therapeutic trials which target adiponectin rely on accurate determination of circulating total and HMW adiponectin levels but the accuracy may be influenced by variations in sample handling processes. The aim of this pilot study was to investigate the effects of delayed processing of blood samples on the concentration of total and HMW adiponectin.</p><p>Materials and Methods: Fasting blood samples were collected for analysis of total and HMW adiponectin concentrations in EDTA plasma and serum from eight healthy participants.  Samples were centrifuged post 15 min storage at 4<sup>o</sup>C as the comparative ‘ideal’ method or after up to 72 h of refrigerated storage or 6 h at room temperature. Total and HMW adiponectin concentrations were measured by ELISA.</p><p>Results: Under ideal handling conditions measurements of total and HMW adiponectin concentrations were significantly higher in serum than in plasma (mean difference: -1.3 µg/mL [95% CI: -1.6, -1.0], p&lt;0.001; and, -0.6 µg/mL [95% CI: -0.7, -0.5], p&lt;0.001, respectively).  Storage of blood samples at 4<sup>o</sup>C for 72 h resulted in significant reductions in concentration of total adiponectin in serum (mean difference: -1.4 µg/mL [95% CI: -2.0, -0.8], p=0.001) and HMW adiponectin in plasma (mean difference: -0.6 µg/mL [95%CI: -0.9, -0.2], p=0.007), compared with ideal conditions.  Further analysis of serum samples showed a significant decrease in total adiponectin concentration after 6 h storage at 4<sup>o</sup>C (mean difference: -1.4 µg/mL [95% CI: -2.0, -0.8], p=0.001) compared with ideal conditions.</p><p>Conclusions: Delayed processing of samples may have differential effects on the concentration of total and HMW adiponectin in serum or plasma. Larger studies are warranted for clinical intervention trials.</p>

Anti carbamylated protein antibodies as a diagnostic marker in patients with rheumatoid arthritis and its association with disease activity

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Magda Medhat Awad El debsy ◽  
Mervat Mohammed Abdul Hakim ◽  
Henaz Farouk Khaled ◽  
Hala Mohamed Abd El Sabour Sabbah
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Plasma Levels ◽  
Significant Positive Correlation ◽  
Diagnostic Marker ◽  
Complete Blood Count ◽  
Control Group ◽  
Positive Correlation ◽  
Larsen Score ◽  
Function Tests

Abstract Background Despite the diagnostic contribution of anti-citrullinated protein( anti-CCP) antibody and rheumatoid factor (RF), approximately one-third of patients with rheumatoid arthritis (RA) remain seronegative .Anti-carbamylated protein (Anti-Carp) antibodies have been attracting increasing attention as a new diagnostic marker of RA. Objective evaluate levels of anti-carp antibodies in RA patients in order to detect its role as a diagnostic marker and its possible association with disease activity and severity. Methods This study included thirty adult patients with clinical evidence of rheumatoid arthritis and thirty healthy matched age and sex as controls. All underwent history taking, clinical examination, assessment of disease activity with modified Disease Activity28 (DAS28), Laboratory investigations including Complete blood count (CBC), erythrocytes sedimentation rate (ESR), C-Reactive Protein (CRP), Liver function tests, Kidney function tests, Serum uric acid, RF, anti CCP Ab, anti-Carp Ab and radiographic Assessment with Larsen score. Results Plasma levels of anti-Carp Ab were significantly higher in patients than control group (p &gt; 0,001) with sensitivity of 73.33% and specificity of 100%.it showed significant positive correlation with CRP (r = 0.37 )(p &lt; 0.05) as a marker of activity of RA and also there was significant positive correlation with RF and ACPA (r = 0.45)(r = 0.48) (p &lt; 0.05) respectively as a diagnostic marker for RA. Plasma levels of anti-Carp Ab were higher in patients with more joints damage and erosions as assessed by Larsen radiological score as there was a highly significant correlation between Larsen score and serum Anti-Carp(r = 0.61)(p &lt; 0.001).. Conclusion serum Anti–Carp antibody level was higher in RA patients which serve as a diagnostic marker for RA, also its significant correlation with CRP and Larsen score may serve as a marker for disease progression and severity.

Insulin-like growth factor (IGF)-II in gastrointestinal stromal tumors (GIST): expression, secretion, and clinical relevance

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20504-20504
Author(s):  
B. Rikhof ◽  
J. van Doorn ◽  
A. Suurmeijer ◽  
M. Rautenberg ◽  
P. Jager ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Growth Factor ◽  
High Molecular Weight ◽  
Plasma Levels ◽  
Islet Cell Tumor ◽  
Disease Status ◽  
High Serum ◽  
Autocrine Growth ◽  
Autocrine Growth Factor

20504 Background: Non-islet cell tumor induced hypoglycemia (NICTH) has been reported anecdotically in patients with a GIST and is associated with increased plasma levels of ‘big’-IGF-II, a high molecular weight form of IGF-II. The role of IGF-II in GIST is unknown. In non- GIST cancer, it has been suggested to be an autocrine growth factor, mainly acting by its major growth promoting receptors IGF-1 receptor (IGF- 1R) and the isoform A of the insulin receptor (IR). We investigated the clinical and biological relevance of (‘big’-)IGF-II in GIST. Methods: Plasma levels of ‘big’-IGF-II, and their relationship with disease status and NICTH, were determined in 25 consecutive GIST patients treated with imatinib (n=24) or sunitinib (n=1). Plasma samples were collected prior to, 1 week, and median 5 months after start of treatment. The levels of ‘big’-IGF-II were measured by specific radioimmunoassay (RIA). Results were compared with those obtained from healthy subjects and expressed as standard deviation scores (SDS). Paraffin-embedded GISTs (n=69) were analyzed for IGF-II, IGF-1R and IR expression by RNA in situ hybridization and immunohistochemistry (IHC). IGF-II secretion by the GIST882 cell line was analyzed by ELISA and western blotting. Results: Before treatment and/or during follow-up, 4 of 25 patients (16%) showed increased (i.e. SDS >2.0) plasma levels of ‘big’-IGF-II. Three of them developed NICTH. Patients with metastatic disease, high serum LDH, or total tumor size >12 cm had the highest ‘big’-IGF-II levels (for all p<0.05). 87% of GISTs expressed IGF-II mRNA, being excessive in tumors from patients with NICTH. These results were confirmed by IHC. GIST882 cells secreted mainly high molecular weight forms of IGF-II. The various GISTs and GIST882 cells did not express IGF-1R or IR. Conclusions: NICTH seems not to be a rare phenomenon in GIST patients. We showed for the first time that most GISTs express and secrete (‘big’-)IGF-II. Therefore, it is likely that many patients are at risk of developing NICTH, presumably especially in case of high tumor bulk. The exact role of (‘big’-)IGF-II in GIST is still not elucidated, as it does not seem to act as an autocrine growth factor since IGF-IR and IR isoform A are lacking. No significant financial relationships to disclose.

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