Are neutrophil extracellular traps the link for the cross-talk between periodontitis and rheumatoid arthritis physiopathology?

Rheumatology ◽  
2021 ◽  
Author(s):  
Sicília Rezende Oliveira ◽  
José Alcides A de Arruda ◽  
Ayda Henriques Schneider ◽  
Valessa Florindo Carvalho ◽  
Caio Machado ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cross Talk ◽  
Neutrophil Extracellular Traps ◽  
Periodontal Therapy ◽  
Clinical Parameters ◽  
Extracellular Traps ◽  
Early Ra ◽  
The Cross ◽  
High Concentrations ◽  
The Impact

Abstract Objectives Neutrophil extracellular traps (NETs) play a role in the pathogenesis of periodontitis and rheumatoid arthritis (RA). However, it remains poorly understood whether NETs participate in the cross-talk between periodontitis and RA. Herein, we investigated the production of NETs in individuals with periodontitis and RA and its association with clinical parameters. The impact of periodontal therapy on RA and NET release was also assessed. Methods The concentration of NETs and cytokines was determined in the saliva and plasma of individuals with early RA (n = 24), established RA (n = 64), and individuals without RA (n = 76). The influence of periodontitis on the production of NETs and cytokines was also evaluated. Results Individuals with early RA had a higher concentration of NETs in saliva and plasma than individuals with established RA or without RA. Periodontitis resulted in an increase in the concentration of NETs of groups of individuals without RA and with early RA. The proportion of individuals with high concentrations of IL-6, IL-10 and GM-CSF was higher among individuals with periodontitis than among individuals without periodontitis. The concentrations of TNF-α, IL-6, IL-17/IL-25, and IL-28A were particularly high in individuals with early RA. Worse periodontal clinical parameters, RA onset and RA activity were significantly associated with circulating NETs. Periodontal therapy was associated with a reduction in the concentration of NETs and inflammatory cytokines and amelioration in periodontitis and RA. Conclusion This study reveals that NETs are a possible link between periodontitis and RA, with periodontal therapy resulting in a dramatic switch in circulating NET levels.

scholarly journals The FcγRIII Engagement Augments PMA-Stimulated Neutrophil Extracellular Traps (NETs) Formation by Granulocytes Partially via Cross-Talk between Syk-ERK-NF-κB and PKC-ROS Signaling Pathways

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1127
Author(s):  
Cheng-Hsun Lu ◽  
Ko-Jen Li ◽  
Cheng-Han Wu ◽  
Chieh-Yu Shen ◽  
Yu-Min Kuo ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Cross Talk ◽  
Neutrophil Extracellular Traps ◽  
Ros Generation ◽  
Dependent Manner ◽  
Extracellular Traps ◽  
Tnf Α ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Polymorphonuclear neutrophils (PMNs) are the most abundant white blood cell in the circulation capable of neutrophil extracellular traps (NETs) formation after stimulation. Both NADPH oxidase-dependent and -independent pathways are involved in NET formation. The IgG is the most abundant immunoglobulin in human serum. However, the impact of the circulating IgG on NET formation is totally unexplored. In this study, the all-trans retinoic acid (ATRA)-induced mature granulocytes (dHL-60) were pre-treated with monomeric human IgG, papain-digested Fab fragment, crystallizable IgG Fc portion, rituximab (a human IgG1), or IgG2. The NET formation of the dHL-60 in the presence/absence of phorbol 12-myristate 13-acetate (PMA) stimulation was then measured by the fluorescent area after SYTOX green nucleic acid stain. The intracellular reactive oxygen species (ROS) generation was measured by flow cytometry. Total and phosphorylated Syk, SHP-1, and ERK were detected by immunoblot. We found that human monomeric IgG and its subclasses IgG1 and IgG2 per se induced negligible NET formation of dHL-60, but the FcγRIII engagement by these IgG subclasses and Fc portion augment PMA-stimulated dHL-60 NET formation in a dose-dependent manner. Furthermore, we found that increased Syk and ERK phosphorylation, intracellular ROS generation, and pro-inflammatory cytokines, IL-8 and TNF-α, production could be induced after FcγRIII engagement. Blocking FcγRIII engagement by a specific antibody diminished the augmented NET formation. In conclusion, we discovered that cross-talk between FcγRIII engagement-induced Syk-ERK and PMA-induced PKC signaling pathways augment NET formation of dHL-60 via increased ROS generation and pro-inflammatory cytokines, IL-8 and TNF-α, production.

scholarly journals AB0048 ENZYMATIC PATTERN OF CIRCULATING PRO- AND ANTIOXIDANT ENZYMES IN RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1056.2-1057
Author(s):  
S. Bedina ◽  
E. Mozgovaya ◽  
A. Trofimenko ◽  
S. Spitsina ◽  
M. Mamus
Keyword(s):  
Rheumatoid Arthritis ◽  
Antioxidant Enzymes ◽  
Disease Activity ◽  
Neutrophil Extracellular Traps ◽  
Unknown Etiology ◽  
Antioxidant Enzyme Activities ◽  
Reference Ranges ◽  
Sod Activity ◽  
Low Disease Activity ◽  
Extracellular Traps

Background:Rheumatoid arthritis (RA) is an autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis and systemic organ involvement resulting in early disability and shorter life expectancy. Neutrophils are suggested to play a substantial role in the induction and promotion of autoimmune inflammation in RA. This ability can be based on newly discovered feature of neutrophils to release neutrophil extracellular traps (NETs) during specific type cell death called NETosis. Hyperproduction of reactive oxygen species (ROS) is one of the factors promoting NETs production. With this background, the study of pro- and antioxidant enzymatic activities in RA patients can be of great interest.Objectives:To assess plasma activities of essential prooxidant and antioxidant enzymes in RA patients.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 71 RA patients (46 women and 25 men) were enrolled in the study. The diagnosis was verified using ACR/EULAR criteria (2010). RA activity was measured using the Disease Activity Score of 28 joints (DAS28). 30 healthy persons comprise control group. Plasma xanthine oxidase (XO; ЕС 1.17.3.2), xanthine dehydrogenase (XDH; ЕС 1.17.1.4) and superoxide dismutase (SOD; ЕС 1.15.1.1) activities were measured using spectrophotometric technique. XO and XDG activities were expressed as nmol/ml/min, SOD activity – as units of action. Statistical analysis was performed using Statistica 6.0 software package. Differences were considered significant when p<0.05. Reference ranges were calculated as means ±2SD.Results:Mean age of patients was 43.2±3.6 years, mean RA duration was 11.9±2.6 years. 24 (33.8%) RA patients had low disease activity, and 6 (8.5%) patients had high one. Extra-articular manifestations were found in 30 (42.2%) patients. 30% of them had cardiovascular involvement, 23.3% – pulmonary lesions, and 23.3% had renal involvement. Reference ranges for XO, XDG, and SOD activities were 2.28-5.12 nmol/min/ml, 3,96-7,24 nmol/min/ml, and 3,13-6,58 units, respectively. We examined activities of these enzymes in circulation of RA patients with different patterns of clinical manifestations as well as relationship between RA activity and XO, XDG, and SOD activities. RA patients had increased both mean XO and mean SOD activities (p<0.001 for both enzymes). XO activity reached its highest values at maximum disease activity and overt extra-articular involvements, while SOD activity did it in moderate and high disease activities as well as in patients with joint manifestations. XDG activity was increased in low disease activity (р<0.001) and solely joint lesions (р=0.011), while moderate or high disease activities (р=0.008) and extra-articular involvements (р=0.025) were characterized by decreased activity of this enzyme.Conclusion:We have revealed substantial multidirectional changes of plasma XO and XDG activities in RA. Plasma enzymatic pattern in RA patients is characterized by activation of both oxidant and antioxidant metabolic pathways. Activities of XO and SOD were positively correlated with RA activity, while XDG activity was negative correlated with RA activity. The differences between selective articular RA type and RA form with extraarticular manifestations were also revealed. Changes in oxidant and antioxidant enzyme activities can be connected with anticitrulline autoimmunity in RA via production of citrulline-rich neutrophil extracellular traps, thus enhancing rheumatoid autoimmunity.Disclosure of Interests:None declared

scholarly journals Disability Related to Function of the Upper Extremities in Early Rheumatoid Arthritis – Course and Relation to Other Disease Parameters Over 10 Years: A Cohort Study

2020 ◽  
Author(s):  
MARIA RYDHOLM ◽  
INGEGERD WIKSTROM ◽  
SOFIA HAGEL ◽  
LENNART T.H. JACOBSSON ◽  
CARL TURESSON
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Grip Force ◽  
Upper Extremities ◽  
Joint Involvement ◽  
Multivariate Linear Regression Analysis ◽  
Clinical Parameters ◽  
Early Ra ◽  
Disease Parameters

Abstract Background: The objective of this study was to investigate the course of disability related to the upper extremities (UE) in early rheumatoid arthritis (RA), and to assess correlations between such disability and clinical parameters, including grip force. Methods: In an inception cohort of patients with early RA (N=222), disability of the UE was assessed using a subscore of the Health assessment questionnaire disability index (HAQ-DI), and average grip force of the dominant hand was measured. Changes between consecutive follow-up visits in the HAQ-DI-UE subscore were assessed using the paired samples t-test, and correlations with key disease parameters using Spearman’s rank test. The relation between joint involvement and HAQ-DI-UE was examined using multivariate linear regression analysis. Results: The HAQ-DI-UE decreased significantly from inclusion to the 6-month follow-up (mean change -0.26; 95% CI -0.18 to -0.34), and increased significantly after 2 years. There were fairly strong correlations for HAQ-DI-UE with grip force (r: -0.50 to -0.62), patient’s global assessment (r:0.58 to 0.64) and patient’s assessment of pain (r:0.54 to 0.60) at all time points up to 5 years, but only moderate to weak correlations with swollen joints, CRP and ESR. At inclusion wrist synovitis and tender PIP joints had both an independent impact on HAQ-DI-UE, whereas tenderness of the shoulder and the wrist had a greater importance at 6 months. Conclusions: Disability related to the upper extremities decreased significantly during the first 6 months, and increased again after 2 years. The correlations with clinical parameters underline the major impact of pain and impaired hand function in early RA.

scholarly journals Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia: secondary analysis of a randomised controlled trial

2018 ◽  
Vol 51 (4) ◽  
pp. 1701389 ◽  
Author(s):  
Fahim Ebrahimi ◽  
Stavros Giaglis ◽  
Sinuhe Hahn ◽  
Claudine A. Blum ◽  
Christine Baumgartner ◽  
...  
Keyword(s):  
Hospital Stay ◽  
Secondary Analysis ◽  
Length Of Hospital Stay ◽  
Neutrophil Extracellular Traps ◽  
Community Acquired Pneumonia ◽  
Extracellular Traps ◽  
Clinical Instability ◽  
Randomised Controlled ◽  
The Impact ◽  
Clinical Stability

Neutrophil extracellular traps (NETs) are a hallmark of the immune response in inflammatory diseases. However, the role of NETs in community-acquired pneumonia (CAP) is unknown. This study aims to characterise the impact of NETs on clinical outcomes in pneumonia.This is a secondary analysis of a randomised controlled, multicentre trial. Patients with CAP were randomly assigned to either 50 mg prednisone or placebo for 7 days. The primary end-point was time to clinical stability; main secondary end-points were length of hospital stay and mortality.In total, 310 patients were included in the analysis. Levels of cell-free nucleosomes as surrogate markers of NETosis were significantly increased at admission and declined over 7 days. NETs were significantly associated with reduced hazards of clinical stability and hospital discharge in multivariate adjusted analyses. Moreover, NETs were associated with a 3.8-fold increased adjusted odds ratio of 30-day mortality. Prednisone treatment modified circulatory NET levels and was associated with beneficial outcome.CAP is accompanied by pronounced NET formation. Patients with elevated serum NET markers were at higher risk for clinical instability, prolonged length of hospital stay and 30-day all-cause mortality. NETs represent a novel marker for outcome and a possible target for adjunct treatments of pneumonia.

scholarly journals Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial)

2009 ◽  
Vol 69 (3) ◽  
pp. 510-516 ◽  
Author(s):  
P Emery ◽  
P Durez ◽  
M Dougados ◽  
C W Legerton ◽  
J-C Becker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Early Stage ◽  
Imaging Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Early Ra ◽  
Acr Criteria ◽  
Very Early Ra ◽  
The Impact

BackgroundSeveral agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA.ObjectiveTo determine the impact of T-cell costimulation modulation in patients with UA or very early RA.MethodsIn this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept (∼10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years.ResultsAt year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) −20.5% (−47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group.ConclusionAbatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease.Trial registration numberNCT00124449.

scholarly journals Non-Surgical Periodontal Therapy Could Improve the Periodontal Inflammatory Status in Patients with Periodontitis and Chronic Hepatitis C

2021 ◽  
Vol 10 (22) ◽  
pp. 5275
Author(s):  
Dorin Nicolae Gheorghe ◽  
Dora Maria Popescu ◽  
Alex Salan ◽  
Mihail Virgil Boldeanu ◽  
Claudiu Marinel Ionele ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Periodontal Therapy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clinical Parameters ◽  
Periodontal Status ◽  
The Impact ◽  
Gingival Fluid ◽  
Chronic Hepatitis C Patients

Non-surgical periodontal therapy (NSPT) is the first essential step for the management of any periodontitis patient. This study aims to evaluate the impact of NSPT on pro-inflammatory mediators’ regulation and on clinical parameters in periodontitis patients who suffer from chronic hepatitis C. At baseline, selected patients were clinically evaluated for their periodontal status. A subsequent quantitative assessment of C-reactive protein and pentraxin-3 in samples of gingival fluid was performed by Enzyme-Linked Immunosorbent Assay (ELISA). Afterwards, NSPT was performed. Three months after NSPT, the clinical and ELISA assessments were repeated. The results show an improvement of the clinical parameters in periodontitis patients at the three-month recall. In chronic hepatitis C patients with periodontitis, the gingival fluid levels of pro-inflammatory markers reduced significantly. The targeted markers also expressed significant correlations with the clinical parameters used for the assessment of periodontitis’ severity. The results suggest that, while chronic hepatitis C patients exhibited a more negative periodontal status at baseline as compared to non-hepatitis ones, NSPT is effective in decreasing the local periodontal inflammatory reaction and in proving the periodontal status of this type of patients. Given the limitation of the study, periodontal screening and NSPT should be included in the integrated therapeutical approach of chronic hepatitis C patients, for its impact on the local inflammatory response.

scholarly journals THE FUNCTIONAL PROPERTIES OF NEUTROPHILS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2015 ◽  
pp. 50-54
Author(s):  
V. V. Zhelezko ◽  
I. A. Novikova
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
Functional Properties ◽  
Blood Cells ◽  
White Blood Cells ◽  
Neutrophil Extracellular Traps ◽  
Functional Class ◽  
Disease Development ◽  
Extracellular Traps ◽  
Functional Features

The article presents the results of the assessment of functional features of neutrophils in 34 patients with rheumatoid arthritis. The study revealed a decrease in absorbing and oxygen producing activity associated with the increased formation of neutrophil extracellular traps (NET) and the dependence of parameters of NET forming activity of white blood cells on the rheumatoid factor, as well as the dependence of spontaneous oxygen producing activity on the functional class and the disease development.

scholarly journals Periodontal therapy increases neutrophil extracellular trap degradation

2019 ◽  
Vol 26 (5) ◽  
pp. 331-340 ◽  
Author(s):  
Carolyn GJ Moonen ◽  
Kirsten GD Buurma ◽  
Mouri RJ Faruque ◽  
Maria G Balta ◽  
Erol Liefferink ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Neutrophil Extracellular Traps ◽  
Periodontal Therapy ◽  
Neutrophil Extracellular Trap ◽  
Polymorphonuclear Leucocytes ◽  
Background Characteristics ◽  
Extracellular Traps ◽  
Inflammatory Status ◽  
Before And After ◽  
Systemic Antibiotics

In periodontitis, polymorphonuclear leucocytes (PMNs) are activated. They entrap and eliminate pathogens by releasing neutrophil extracellular traps (NETs). Abnormal NET degradation is part of a pro-inflammatory status, affecting co-morbidities such as cardiovascular disease. We aimed to investigate the ex vivo NET degradation capacity of plasma from periodontitis patients compared to controls (part 1) and to quantify NET degradation before and after periodontal therapy (part 2). Fresh NETs were obtained by stimulating blood-derived PMNs with phorbol 12-myristate 13-acetate. Plasma samples from untreated periodontitis patients and controls were incubated for 3 h onto freshly generated NETs (part 1). Similarly, for part 2, NET degradation was studied for 91 patients before and 3, 6 and 12 mo after non-surgical periodontal therapy with and without adjunctive systemic antibiotics. Finally, NET degradation was fluorospectrometrically quantified. NET degradation levels did not differ between periodontitis patients and controls, irrespective of subject-related background characteristics. NET degradation significantly increased from 65.6 ± 1.7% before periodontal treatment to 75.7 ± 1.2% at 3 mo post periodontal therapy, and this improvement was maintained at 6 and 12 mo, irrespective of systemic usage of antibiotics. Improved NET degradation after periodontitis treatment is another systemic biomarker reflecting a decreased pro-inflammatory status, which also contributes to an improved cardiovascular condition.

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