scholarly journals Serum Levels of Asymmetric Dimethylarginine and Apelin as Potential Markers of Vascular Endothelial Dysfunction in Early Rheumatoid Arthritis

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Manuela Di Franco ◽  
Francesca Romana Spinelli ◽  
Alessio Metere ◽  
Maria Chiara Gerardi ◽  
Virginia Conti ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Dysfunction ◽  
Asymmetric Dimethylarginine ◽  
Inflammatory Diseases ◽  
Early Stage ◽  
Serum Levels ◽  
Joint Disease ◽  
Baseline Serum ◽  
Before And After ◽  
Treatment Naïve

Objectives. Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA). As modulators of endothelial nitric oxide synthase expression, asymmetric-dimethylarginine (ADMA) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA) before and after disease-modifying antirheumatic drug (DMARD) therapy.Methods. We enrolled 20 consecutively diagnosed, treatment-naïve patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28) were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT) evaluation.Results. In the ERA group, ADMA serum levels were significantly higher than controls at baseline(P=0.007)and significantly decreased after treatment (P=0.012versus controls). Baseline serum apelin levels were significantly decreased in this group (P=0.0001versus controls), but they were not significantly altered by treatment. IMT did not show significant changes.Conclusions. ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients.

scholarly journals OP0035 ASSESSMENT OF THE INTESTINAL PERMEABILITY IN PATIENTS WITH RHEUMATOID ARTHRITIS USING COLONIC TISSUES AND SERA

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 19.2-19
Author(s):  
R. Audo ◽  
P. Sanchez ◽  
J. Mielle ◽  
L. Macia ◽  
B. Rivière ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Intestinal Permeability ◽  
Systemic Inflammation ◽  
Inflammatory Diseases ◽  
Staining Intensity ◽  
Serum Markers ◽  
Before And After ◽  
Colonic Biopsies ◽  
Junction Proteins

Background:Patients with rheumatoid arthritis (RA) have an altered gut microbiota (dysbiosis) (1-3). This microbiota interacts with intestinal epithelium which can lead to an increased intestinal permeability, responsible for the passage of antigens and inflammatory molecules, and can therefore promote systemic inflammation. Gut microbiota tends to normalize with disease control (2), suggesting that systemic inflammation may directly influence the composition of microbiota and the gut barrier. It was shown in many inflammatory diseases that intestinal permeability is impaired, but to date there is very little data in RA.Objectives:In the present study, we evaluate the intestinal permeability in RA patients by analyzing tight junctions in colonic biopsies and serum markers.Methods:Colonic biopsies from 20 RA patients who underwent coloscopy for screening with normal histology were compared with those from 20 age and sex matched controls. ZO-1, occludin and claudin 2 junction proteins were evaluated by immunohistochemistry. The staining intensity was assessed by two blinded independent readers. The serum concentrations of LPS-binding protein (LBP), CD14s and zonulin were evaluated by ELISA in 25 patients naive of DMARDs, 41 patients before and after introduction of a DMARDs and 21 controls. Elevated zonulin in serum indicates an increase in intestinal permeability while LBP and CD14s indicate bacterial translocation.Results:ZO-1 expression was significantly lower in biopsies from patients with RA than controls (mean score ± SD of 1.6 ± 0.56 vs 2.0 ± 0.43; p = 0.01). Age, sex, disease duration and immunological status did not significantly influence the expression of colonic junction proteins. LBP and CD14s were higher in serum from RA patients naive of DMARDs than controls (p = 0.002 and p = 0.003). LBP, CD14s and zonulin levels significantly correlated with DAS28 (r = 0.61, p = 0.005; r = 0.51, p = 0.030 and r = 0.46, p = 0.049, respectively). After treatment, unlike non-responders, LBP and CD14s were significantly reduced in DMARD responders and variations in LBP and CD14s significantly correlated with changes in DAS28 (r = 0.46, p = 0.002 and r = 0, 33 and p = 0.030, respectively).Conclusion:This work is one of the first to explore intestinal permeability in RA and to show altered tight junction in colonic tissue from RA. This increased intestinal permeability appears to be related to the systemic inflammation. Improving the gut microbiota through food or probiotics could enhance the effect of treatments by limiting this amplification loop of inflammation.References:[1]Horta-Baas G, Romero-Figueroa MDS, Montiel-Jarquin AJ, Pizano-Zarate ML, Garcia-Mena J, Ramirez-Duran N. Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis. J Immunol Res. 2017;2017:4835189.[2]Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895-905.[3]Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, et al. Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine. Arthritis Rheumatol. 2016;68(11):2646-61.Disclosure of Interests:Rachel Audo: None declared, Pauline Sanchez: None declared, Julie Mielle: None declared, Laurence Macia: None declared, Benjamin Rivière: None declared, Cédric Lukas: None declared, Bernard Combe: None declared, Jacques Morel: None declared, Claire Daien Speakers bureau: Pfizer roche chugai fresenius BMS msd Novartis galapagos, Consultant of: Abivax abbbvie BMS roche chugai, Grant/research support from: Pfizer, roche-chugai, fresenius, msd

scholarly journals Sexual Dimorphisms of Adrenal Steroids, Sex Hormones, and Immunological Biomarkers and Possible Risk Factors for Developing Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Alfonse T. Masi ◽  
Azeem A. Rehman ◽  
Laura C. Jorgenson ◽  
Jennifer M. Smith ◽  
Jean C. Aldag
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Sexual Dimorphism ◽  
Sex Hormones ◽  
Inflammatory Diseases ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Serum Levels ◽  
Amyloid A ◽  
Neuroendocrine Factors

Innate immunity and immunological biomarkers are believed to be interrelated with sex hormones and other neuroendocrine factors. Sexual dimorphism mechanisms may be operating in certain rheumatic and inflammatory diseases which occur more frequently in women than men, as rheumatoid arthritis (RA). Less data have been available on altered interrelations of the combined neuroendocrine and immune (NEI) systems as risk factors for development of certain diseases. In this study, serological interrelations of NEI biomarkers are analyzed before symptomatic onset of RA (pre-RA) versus control (CN) subjects, stratified by sex. Sexual dimorphism was found in serum levels of acute serum amyloid A (ASAA), soluble interleukin-2 receptor alpha (sIL-2Rα), and soluble tumor necrosis factor receptor 1 (sTNF-R1). Multiple steroidal and hormonal (neuroendocrine) factors also showed highly(p<0.001)significant sexual dimorphism in their assayed values, but less for cortisol(p=0.012), and not for 17-hydroxyprogesterone(p=0.176). After stratification by sex and risk of developing RA, differential NEI correlational patterns were observed in the interplay of the NEI systems between the pre-RA and CN groups, which deserve further investigation.

scholarly journals Features of biochemical indices and content of enzymes in the serum of syphilis patients with viral hepatites B and C in the course of treatment

2021 ◽  
Vol 26 (3) ◽  
pp. 107-113
Author(s):  
S.V. Zakharov ◽  
V.K. Zakharov ◽  
V.V. Gorbuntsov
Keyword(s):  
Functional State ◽  
Biochemical Parameters ◽  
Early Stage ◽  
Serum Levels ◽  
Test Methods ◽  
Comprehensive Examination ◽  
Before And After ◽  
Biochemical Indices ◽  
Increased Activity ◽  
Latent Syphilis

Objective – before and after the treatment to determine the functional state of the liver, serum levels of enzymes and biochemical indices in syphilis patients with viral hepatites B and C. The results of the study are based on the data from a comprehensive examination of 35 patients with syphilis alone and 127 patients with syphilis co-infected with viral hepatites B and C before and after treatment. Test methods: hepatology, rheogeopathography, enzyme content and biochemical parameters determined in the serum. According to the results of radionuclide hepatology it has been established that disorders of the functional capacity of the liver already occur in the early stages of the disease. The most significant disorders have been in the patients with the prescription of infection for more than 12 months and in the patients co-infected with viral hepatites B and C. A disorder of pigment metabolism and increased activity of trans­aminases have been revealed in early latent syphilis. In co-infection with viral hepatites B and C an increase in total bilirubin, Lactate dehydrogenase, Alanine transaminase, Aspartate aminotransferase and albumin has been revealed. Dysproteinemia has been revealed in patients with early latent syphilis co-infected with hepatitis C. Patients with early latent syphilis treated with immunomodulators tend to normalize these indices. In patients with syphilis a disorder of the functional state of the liver have been revealed already at an early stage of the disease. The most pronounced disorder of biochemical parameters and activity of liver enzymes are observed in syphilis patients with viral hepatites B and C, as well as in patients with early latent syphilis only with the prescription of the infection for more than 12 months; in such a case it is advisable to use drugs affecting the immune system.

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 Significance of Circulating and Crevicular Matrix Metalloproteinase-9 in Rheumatoid Arthritis-Chronic Periodontitis Association

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Isabela Silosi ◽  
Manole Cojocaru ◽  
Lili Foia ◽  
Mihail Virgil Boldeanu ◽  
Florin Petrescu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chronic Periodontitis ◽  
Gingival Crevicular Fluid ◽  
Serum Levels ◽  
Joint Disease ◽  
Control Serum ◽  
Healthy Control ◽  
Crevicular Fluid ◽  
And Control ◽  
Metalloproteinase 9

In the recent years, statistically significant associations between rheumatoid arthritis (RA) and periodontal disease have been identified. Emerging as a chronic inflammatory joint disease, RA displays various features and pathogenetic events similar to chronic periodontitis (CP). The purpose of this study was to evaluate the utility of determining systemic and crevicular levels of metalloproteinase-9 (MMP-9) as potential biomarkers for association between RA and CP. A total of fifty-six patients were included in the study. The subjects were categorized into four groups as follows: healthy-control (n=21), active RA (n=16), CP (n=14), and RA-CP association (n=12). Assessment of serum and crevicular concentrations of total MMP-9 (active and pro-MMP-9) was based on ELISA technique. The results of this study showed statistically significant differences of serum MMP-9 between patients groups and control. Serum levels of MMP-9 were similar in RA and RA-CP associated patients. Gingival crevicular fluid (GCF) recorded increased MMP-9 levels in RA-CP association subjects as compared to CP. Considering that RA-CP association is characterized by a disregulation of the inflammatory response, MMP-9 may play a role in the pathogenesis of RA-CP association. MMP-9 is therefore a sensitive tool in the diagnosis and management of patients affected by this binomial association.

scholarly journals The Efficacy of Moxibustion on the Serum Levels of CXCL1 and β-EP in Patients with Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Siyu Tao ◽  
Xue Wang ◽  
Chenxi Liao ◽  
Yan Xiong ◽  
Jie Tang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Therapy ◽  
Treatment Group ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Control Group ◽  
Tnf Α ◽  
Before And After ◽  
Chemokine Ligand ◽  
Pain Symptoms

Objective. This study aims to evaluate the efficacy of moxibustion on joint swelling and pain and the levels of C-X-C motif chemokine ligand 1 (CXCL1), β-endorphin (β-EP) in serum of rheumatoid arthritis (RA) patients and to investigate the anti-inflammatory and analgesic mechanism of moxibustion on improving RA. Methods. Sixty-eight patients with RA were randomly and equally classified into the control and treatment groups. The control group was treated with routine drug therapy, while the treatment group received routine drug therapy and moxibustion. Both groups were treated for eight weeks. The symptoms and laboratory indicators of RA patients were compared in the two groups before and after intervention. Results. Sixty-one patients completed the study: four patients dropped out from the treatment group and three from the control group. Trial endpoints were change (∆) in symptoms, measured by Ritchie’s articular index (RAI), swollen joint count (SJC), and laboratory indicators, measured by the level of CXCL1, β-EP, tumor necrosis factor-a (TNF-α), and interleukin-1β (IL-1β). ∆RAI, ∆SJC, ∆CXCL1, ∆β-EP, ∆TNF-α, and ∆IL-1β in the treatment group were superior to the control group (13.50 [14.50] versus 6.00 [13.00] in ∆RAI, 4.00 [3.00] versus 2.00 [4.00] in ∆SJC, 0.04 ± 0.79 ng/mL versus -0.01 ± 0.86 ng/mL in ∆CXCL1, -2.43 [5.52] pg/mg versus -0.04 [4.09] pg/mg in ∆β-EP, 3.45 [5.90] pg/mL versus 1.55 [8.29] pg/mL in ∆TNF-α, and 6.15 ± 8.65 pg/mL versus 1.28 ± 8.51 pg/mL in ∆IL-1β; all P  < 0.05). Conclusion. Moxibustion can improve the joint swelling and pain symptoms in patients with RA, which may be related to the fact that moxibustion can reduce the release of inflammatory factors in patients with RA and downregulate the level of CXCL1 and increase the level of β-EP at the same time. This trial is registered with ChiCTR-IOR-17012282.

Asymmetric dimethylarginine: a key player in the pathophysiology of endothelial dysfunction, vascular inflammation and atherosclerosis in rheumatoid arthritis?

2021 ◽  
Vol 27 ◽  
Author(s):  
Arduino A Mangoni ◽  
Sara Tommasi ◽  
Salvatore Sotgia ◽  
Angelo Zinellu ◽  
Panagiotis Paliogiannis ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Dysfunction ◽  
Asymmetric Dimethylarginine ◽  
Vascular Inflammation ◽  
Good Evidence ◽  
Plaque Deposition ◽  
Pathophysiological Role ◽  
Autoimmune Condition ◽  
And Oxidative Stress

: Patients with rheumatoid arthritis (RA), a chronic and disabling autoimmune condition that is characterized by articular and extra-articular manifestations and a pro-inflammatory and pro-oxidant state, suffer from premature atherosclerosis and excessive cardiovascular disease burden. A key step in the pathogenesis of atherosclerosis is the impaired synthesis of the endogenous messenger nitric oxide (NO) by endothelial cells which, in turn, alters local homeostatic mechanisms and favors vascular damage and plaque deposition. While the exact mechanisms of endothelial dysfunction in RA remain to be established, there is good evidence that RA patients have relatively high circulating concentrations of the methylated arginine asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of endothelial NO synthase (eNOS). This review discusses the biological and pathophysiological role of ADMA, the interplay between ADMA, inflammation and oxidative stress, and the available evidence on the adverse impact of ADMA on endothelial function and atherosclerosis and potential ADMA-lowering therapies in RA patients.

scholarly journals Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes

2019 ◽  
Vol 20 (16) ◽  
pp. 4046 ◽  
Author(s):  
Valerie R. Wiersma ◽  
Alex Clarke ◽  
Simon D. Pouwels ◽  
Elizabeth Perry ◽  
Trefa M. Abdullah ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Levels ◽  
Arginine Deiminase ◽  
Joint Disease ◽  
Protein Levels ◽  
Reactive Protein ◽  
Peptidyl Arginine Deiminase ◽  
Key Enzyme ◽  
Immunomodulatory Protein

The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.

scholarly journals Pathophysiological Role of Adiponectin, Leptin and Asymmetric Dimethylarginine in the Process of Atherosclerosis

Folia Medica ◽  
2016 ◽  
Vol 58 (4) ◽  
pp. 234-240 ◽  
Author(s):  
Daniela Iv. Koleva ◽  
Maria M. Orbetzova ◽  
Julia G. Nikolova ◽  
Tanya I. Deneva
Keyword(s):  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Proinflammatory Cytokines ◽  
Asymmetric Dimethylarginine ◽  
Serum Levels ◽  
Reactive Protein ◽  
Proinflammatory Mediators ◽  
Pathophysiological Role

Abstract Adipose tissue is recognized as a rich source of proinflammatory mediators that may directly contribute to vascular injury, insulin resistance, and atherogenesis. Many studies have shown that adiponectin has antiatherogenic and anti-inflammatory properties. Adiponectin acts not only as a factor increasing insulin sensitivity, and the protective effect may result from its ability to suppress production of proinflammatory cytokines. It negatively regulates the expression of TNF-alpha and C-reactive protein (CRP) in adipose tissue; reduces expression of vascular and intracellular adhesion molecules (VCAM-1, ICAM-1), E-selectin, interleukin-8 (IL-8). Hyperleptinemia has been linked with the development of hypertension and endothelial dysfunction/atherosclerosis, two main pathophysiological conditions associated with cardiovascular disease development. Leptin-mediated increases in sympathetic nervous system activity may be among the principal mechanisms evoking obesity related hypertension. Leptin stimulates the secretion of proinflammatory cytokines, and increases the release of endothelin-1 (ET-1), which may promote hypertension. Increased serum levels of asymmetric dimethylarginine (ADMA), a physiological regulator of the biosynthesis of nitric oxide (NO), promote the process of atherosclerosis, leading to the occurrence of endothelial dysfunction and cardiovascular disease.

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