scholarly journals Rheumatoid arthritis synovial fluid neutrophils drive inflammation through production of chemokines, reactive oxygen species and neutrophil extracellular traps

2020 ◽  
Author(s):  
Helen L Wright ◽  
Max Lyon ◽  
Elinor A Chapman ◽  
Robert J Moots ◽  
Steven W Edwards
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Neutrophil Migration ◽  
Joint Damage ◽  
Inflammatory Disorder ◽  
Ros Production ◽  
Chronic Inflammatory Disorder ◽  
Adaptive Immune Cells ◽  
Activated Neutrophils ◽  
Healthy Control

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Neutrophils are believed to play an important role in both the initiation and progression of RA, and large numbers of activated neutrophils are found within both synovial fluid (SF) and synovial tissue from RA joints. In this study we analysed paired blood and SF neutrophils from patients with severe, active RA (DAS28>5.1, n=3) using RNA-seq. 772 genes were significantly different between blood and SF neutrophils. IPA analysis predicted that SF neutrophils had increased expression of chemokines and ROS production, delayed apoptosis, and activation of signalling cascades regulating the production of NETs. This activated phenotype was confirmed experimentally by incubating healthy control neutrophils in cell-free RA SF, which was able to delay apoptosis and induce ROS production in both unprimed and TNFα primed neutrophils (p<0.05). RA SF significantly increased neutrophil migration through 3μM transwell chambers (p<0.05) and also increased production of NETs by healthy control neutrophils, including exposure of myeloperoxidase (MPO) and citrullinated histone-H3-positive DNA NETs. IPA analysis predicted NET production was mediated by signalling networks including AKT, RAF1, SRC and NF-κB. Our results expand the understanding of the molecular changes that take place in the neutrophil transcriptome during migration into inflamed joints in RA, and the altered phenotype in RA SF neutrophils. Specifically, RA SF neutrophils lose their migratory properties, residing within the joint to generate signals that promote joint damage, as well as inflammation via recruitment and activation of both innate and adaptive immune cells. We propose that this activated SF neutrophil phenotype contributes to the chronic inflammation and progressive damage to cartilage and bone observed in patients with RA.

scholarly journals Rheumatoid Arthritis Synovial Fluid Neutrophils Drive Inflammation Through Production of Chemokines, Reactive Oxygen Species, and Neutrophil Extracellular Traps

2021 ◽  
Vol 11 ◽  
Author(s):  
Helen L. Wright ◽  
Max Lyon ◽  
Elinor A. Chapman ◽  
Robert J. Moots ◽  
Steven W. Edwards
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Neutrophil Migration ◽  
Joint Damage ◽  
Inflammatory Disorder ◽  
Ros Production ◽  
Chronic Inflammatory Disorder ◽  
Adaptive Immune Cells ◽  
Activated Neutrophils ◽  
Healthy Control

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Neutrophils are believed to play an important role in both the initiation and progression of RA, and large numbers of activated neutrophils are found within both synovial fluid (SF) and synovial tissue from RA joints. In this study we analyzed paired blood and SF neutrophils from patients with severe, active RA (DAS28&gt;5.1, n=3) using RNA-seq. 772 genes were significantly different between blood and SF neutrophils. IPA analysis predicted that SF neutrophils had increased expression of chemokines and ROS production, delayed apoptosis, and activation of signaling cascades regulating the production of NETs. This activated phenotype was confirmed experimentally by incubating healthy control neutrophils in cell-free RA SF, which was able to delay apoptosis and induce ROS production in both unprimed and TNFα primed neutrophils (p&lt;0.05). RA SF significantly increased neutrophil migration through 3μM transwell chambers (p&lt;0.05) and also increased production of NETs by healthy control neutrophils (p&lt;0.001), including exposure of myeloperoxidase (MPO) and citrullinated histone-H3-positive DNA NETs. IPA analysis predicted NET production was mediated by signaling networks including AKT, RAF1, SRC, and NF-κB. Our results expand the understanding of the molecular changes that take place in the neutrophil transcriptome during migration into inflamed joints in RA, and the altered phenotype in RA SF neutrophils. Specifically, RA SF neutrophils lose their migratory properties, residing within the joint to generate signals that promote joint damage, as well as inflammation via recruitment and activation of both innate and adaptive immune cells. We propose that this activated SF neutrophil phenotype contributes to the chronic inflammation and progressive damage to cartilage and bone observed in patients with RA.

Interleukin-34 in the Serum and Synovial Fluid of Rheumatoid Arthritis Patients: Relation to Disease Activity and Radiographic Damage

2018 ◽  
Vol 58 (01) ◽  
pp. 65-70 ◽  
Author(s):  
Zahraa Selim ◽  
Sonya Rashad ◽  
Marwa Abdelaziz ◽  
Shaimaa Salah ◽  
Doaa Fouad ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Joint Damage ◽  
Bone Destruction ◽  
Radiographic Damage ◽  
Healthy Control ◽  
Radiological Damage ◽  
Arthritic Joints

Abstract Background Interleukin 34 (IL-34) is a recently discovered proinflammatory cytokine that can promote inflammation and osteoclastogenesis in arthritic joints. In this study, we tried to assess the serum and synovial fluid (SF) levels of IL-34 in rheumatoid arthritis (RA) patients, and to determine its relationship with disease activity and radiographic damage. Patients and methods ELISA was used to evaluate IL-34 levels in the serum of RA patients (n=50), osteoarthritis (OA) patients (n=28), and healthy control subjects (n=20) and in SF isolated from RA and OA patients. Disease activity in RA patients was assessed using the disease activity score-28 (DAS 28). The extent of radiographic joint damage, narrowing, and erosions was assessed. Results Serum IL-34 level was significantly elevated in RA patients compared to that in OA patients and healthy controls (P<0.0001). Synovial IL-34 level was also significantly elevated in RA patients compared to that in OA patients (P=0.0004). Serum and synovial IL-34 levels were significantly higher in cases that were rheumatoid factor (RF) positive (n=28) compared to the levels in RF-negative RA cases (n=22) (P=0.03 and P=0.04, respectively). Serum and synovial IL-34 levels were positively correlated with RF (r=0.43, P=0.02 and r=0.39, P=0.03, respectively), and with the extent of radiological damage (SENS) (P=0.0002 and P<0.0001, respectively). However, no significant correlation between IL-34 levels and disease activity was found. Conclusion IL-34 appears to play a key role in the pathogenesis of RA and contribute to bone destruction, making it a potential therapeutic target in the management armamentarium of the disease.

scholarly journals Molecular characterisation of the synovial fluid microbiome in rheumatoid arthritis patients and healthy control subjects

PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0225110 ◽  
Author(s):  
Dargham Bayan Mohsen Hammad ◽  
Veranja Liyanapathirana ◽  
Daniel Paul Tonge
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Molecular Characterisation ◽  
Control Subjects ◽  
Healthy Control

A Severe Necrotizing Inflammatory Reaction of Leg Wounds Following Autologous Peripheral Blood Total Nucleated Cells Treatment in an Old Patient With Rheumatoid Arthritis and No-Option Chronic Limb-Threatening Ischemia: Is Cell Therapy Suitable for All Patients?

2021 ◽  
pp. 153473462199757
Author(s):  
Valerio Vallini ◽  
Luigi Venturini ◽  
Paolo Carnesecchi ◽  
Roberto Andreini ◽  
Simone Meini
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Therapy ◽  
Inflammatory Reaction ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Inflammatory Disorder ◽  
Skin Atrophy ◽  
Chronic Inflammatory Disorder ◽  
Increased Risk

Chronic limb-threatening ischemia (CLTI) represents an unfavorable evolution of peripheral artery disease, characterized by pain at rest, ulceration, and gangrene and also by an increased risk of cardiovascular events, amputations, and death. According to scientific literature, in almost one third of cases affected by CLTI, defined as no-option CLTI patients, revascularization strategies are not feasible. In the past decade, several studies investigated the role of therapeutic angiogenesis through cell autologous therapy, administered through intramuscular injections or multiple local intralesional and perilesional injections. In this article, we report the case of a necrotizing inflammatory reaction in a patient affected by CLTI and chronic leg wounds that occurred on the multiple injection sites after autologous peripheral blood-derived mononuclear cells (PB-TNCs) transplantation. Since the patient was affected by corticosteroid-induced skin atrophy and rheumatoid arthritis, we hypothesize that an increased skin fragility and a mechanism of immune-mediated pathergy could have been main factors leading to worsening of wounds. This case report strongly suggests the urgent need to better define the indications and contraindications of cell therapy, and further studies of adequate methodology are required to definitively assess the efficacy and safety of autologous cell therapy by local injections of PB-TNCs in patients with chronic inflammatory disorder, such as rheumatoid arthritis, especially in case of concomitant marked skin atrophy. Pending definitive evidence from literature, a strong caution is needed in patients affected by chronic systemic inflammatory diseases, since multiple injections, acting as mechanical stimulus and pathergy trigger, might exacerbate a severe and uncontrolled inflammatory response.

scholarly journals Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint

2021 ◽  
Author(s):  
Fiona R Macfarlane ◽  
Mark AJ Chaplain ◽  
Raluca Eftimie
Keyword(s):  
Rheumatoid Arthritis ◽  
Numerical Simulations ◽  
Model Parameters ◽  
Inflammatory Disorder ◽  
Pannus Formation ◽  
Chronic Inflammatory Disorder ◽  
Modelling Framework ◽  
Small Joint ◽  
Pip Joint ◽  
The Impact

AbstractRheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, swelling and stiffness in the joints, and negatively impacts the life of affected patients. The disease does not have a cure yet, as there are still many aspects of this complex disorder that are not fully understood. While mathematical models can shed light on some of these aspects, to date there are not many such models that can be used to better understand the disease. As a first step in the mechanistic understanding of RA, in this study we introduce a new hybrid mathematical modelling framework that describes pannus formation in a small proximal interphalangeal (PIP) joint. We perform numerical simulations with this new model, to investigate the impact of different levels of immune cells (macrophages and fibroblasts) on the degradation of bone and cartilage. Since many model parameters are unknown and cannot be estimated due to a lack of experiments, we also perform a sensitivity analysis of model outputs to various model parameters (single parameters or combinations of parameters). Finally, we connect our numerical results with current treatments for RA, by discussing our numerical simulations in the context of various drug therapies using, for example, methotrexate, TNF-inhibitors or tocilizumab, which can impact different model parameters.

The Influence of Rheumatoid Arthritis on Work Productivity among a Sample of Iraqi Patients

2021 ◽  
Vol 1 ◽  
pp. 110-117
Author(s):  
Faiq Isho Gorial ◽  
Sattar Jabbar Naema ◽  
Hameed Oda Ali ◽  
Saad Abdulrahman Hussain
Keyword(s):  
Rheumatoid Arthritis ◽  
Work Productivity ◽  
Control Group ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Daily Life Activities ◽  
Rheumatology Unit ◽  
Medical City ◽  
The Impact ◽  
Control Study

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder that impact daily life activities. The impact on work productivity is critical because of persistent work disability. Aim: To evaluate work productivity in RA patients compared to healthy controls, and to assess the impact of socio-demographic characteristics on work productivity. Methods: This was a case-control study conducted at the Rheumatology Unit of Baghdad Teaching Hospital, Medical City during the period from August 2020 to the end of March 2021. Seventy-two patients with RA were selected and compared with 72 healthy subjects as a control group. All patients were diagnosed according to ACR/EULAR 2010 RA classification criteria. The socio-demographic and clinical features, lifestyle practices, and disease activity of the patients and controls were all recorded during interviews. A standardized Arabic version of the Workplace Activity Limitation Scale (WALS) and the Job Limitations Questionnaire were used to assess the impact of RA on work productivity (WLQ-25). Results: The vast majority of patients were females (58.1%). Positive rheumatoid factor was reported in 94.4% of the patients. The patients showed a significantly lower WALS total score and higher WLQ-25 total score median (IQR) compared with controls. Conclusion: Active RA impairs the work productivity which was influenced by CDAI score and negatively associated with the use of DMARDs.

Joint Ventures: Helping Those With Rheumatoid Arthritis Live Well

2013 ◽  
Vol 23 (2) ◽  
pp. 91-100 ◽  
Author(s):  
Aggie Stewart
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Stress Reduction ◽  
Symptom Relief ◽  
Well Being ◽  
Inflammatory Disorder ◽  
Yoga Therapy ◽  
Chronic Inflammatory Disorder ◽  
Stiffness Loss

Objectives: Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory disorder that causes pain, swelling, stiffness, loss of joint function, and reduced quality of life. Yoga therapy may help individuals with RA manage stress and increase well-being. This study focused on the identification of therapeutic objectives and a methodology to achieve symptom relief, regain function, and enhance quality of life for individuals with RA. Methods: Four women with RA participated in private yoga therapy sessions for 2.5 months. Assessment based, tailored home practices were developed and modified to address participant - identified goals. Results: Participants reported decreased pain, fatigue, swelling, and flares; increased energy; pain-free range of motion and strength around affected joints; and a heightened sense of well-being. Conclusions: Tailored yoga therapy that emphasizes stress reduction may be beneficial for individuals with RA.

Evaluation of Some Immunological Marker for Early Diagnosis of Rheumatoid Arthritis

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Israa K AL- Yasiri ◽  
Israa K AL- Yasiri ◽  
Jaafar K Al-Mousawi ◽  
Ali M.Al Mohana
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Interleukin 1 ◽  
Joint Damage ◽  
Serological Marker ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Significant Difference ◽  
Healthy Control

Rheumatoid arthritis (RA) is a chronic,destructive autoimmune disease affecting the joints. With more sophisticated and effective therapies becoming available and with the understanding that early intervention is crucial in preventing irreversible joint damage,it is more and more important to diagnose RA at a very early stage in the disease. To facilitate diagnosis during the early stages of the disease,when often not all clinical symptoms are manifest,a good serological marker is needed. The main purpose of this observational study was to evaluate and detects a good serological marker and genetic factors may be used in early detection of RA. This study covers quite different regions of Najaf province,including rural and urban communities. During the period from May 2010 to May2011,a total of 40 patients with RA who were fulfilled four or more of the 1987 American College of Rheumatology (ACR),20 patients with joints problems (JP),20 RA patient relatives (PR) and 10 apparently healthy control individuals were included in this study. Cytokines (interleukin-1,IL-6,IL-10 and TNF ɑ),antibodies directed to cyclic citrullinated peptide (anti-CCP3),and anti-human immunoglobulin binding protein (anti-BiP) antibodies in the human serum samples were measured by enzyme-linked immunosorbent assay (ELISA). Thirty-two RA patients (80.0%) were positive for anti-CCP3,whereas only 20.0%,30.0% and 0.0% showed a positive reaction,in particular sera from PR,JP and healthy control,respectively with highly significant difference was observed. The mean serum anti-CCP3 antibody level was higher in RA patients than in other groups. The anti-BiP antibody levels were significantly increased in RA patients than in PR and healthy control. However,the levels of anti-BiP antibody were slightly increased in the JP and no significant difference was detected between RA patients and JP. Analysis of the serum samples showed that concentrations of the Proinflammatory cytokines,IL-1,IL-6 and TNFɑ were significantly increased in RA patients compared with matched control subjects. While,The level of IL-10 was significantly lower for RA patients than for healthy Control cases.

scholarly journals Hydrogels in the treatment of rheumatoid arthritis: drug delivery systems and artificial matrices for dynamic in vitro models

2021 ◽  
Vol 32 (7) ◽  
Author(s):  
Isabel Maria Oliveira ◽  
Diogo Castro Fernandes ◽  
Ibrahim Fatih Cengiz ◽  
Rui Luís Reis ◽  
Joaquim Miguel Oliveira
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
In Vitro Models ◽  
Delivery Systems ◽  
Disease Models ◽  
Inflammatory Disorder ◽  
Tissue Destruction ◽  
Animal Testing ◽  
Chronic Inflammatory Disorder

AbstractRheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disorder that mostly affects the synovial joints and can promote both cartilage and bone tissue destruction. Several conservative treatments are available to relieve pain and control the inflammation; however, traditional drugs administration are not fully effective and present severe undesired side effects. Hydrogels are a very attractive platform as a drug delivery system to guarantee these handicaps are reduced, and the therapeutic effect from the drugs is maximized. Furthermore, hydrogels can mimic the physiological microenvironment and have the mechanical behavior needed for use as cartilage in vitro model. The testing of these advanced delivery systems is still bound to animal disease models that have shown low predictability. Alternatively, hydrogel-based human dynamic in vitro systems can be used to model diseases, bypassing some of the animal testing problems. RA dynamic disease models are still in an embryonary stage since advances regarding healthy and inflamed cartilage models are currently giving the first steps regarding complexity increase. Herein, recent studies using hydrogels in the treatment of RA, featuring different hydrogel formulations are discussed. Besides, their use as artificial extracellular matrices in dynamic in vitro articular cartilage is also reviewed.

scholarly journals T cell immunoglobulin and mucin domain-3 is associated with disease activity and progressive joint damage in rheumatoid arthritis patients

2020 ◽  
Author(s):  
Haruki Matsumoto ◽  
Yuya Fujita ◽  
Tomoyuki Asano ◽  
Naoki Matsuoka ◽  
Jumpei Temmoku ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Disease Activity ◽  
Joint Damage ◽  
Serum Levels ◽  
Matrix Metalloproteinase 3 ◽  
Surface Molecules ◽  
Healthy Control ◽  
Domain 3

Abstract Background T cell immunoglobulin and mucin domain-3 (TIM-3) is a surface molecules expressed on immune cells which play a role in immune regulation. The aims of the present study were to determine whether circulating soluble T cell immunoglobulin and mucin domain-3 (sTIM-3) is elevated in rheumatoid arthritis (RA) patients, and investigate the relationships between sTIM-3 and clinical features of RA. Methods The study included 116 patients with established RA and 27 healthy control subjects. Serum levels of sTIM-3 were measured via the enzyme-linked immunosorbent assays (ELISA). Correlations between serum sTIM-3 and a range of parameters including ACPA titer, erythrocyte sedimentation rate (ESR) and matrix metalloproteinase-3 (MMP-3) were assessed. Results Serum sTIM-3 was significantly elevated in RA patients compared with healthy subjects, and it was positively correlated with ACPA titer (r = 0.27 p = 0.005), ESR (r = 0.27, p = 0.004) and MMP-3 (r = 0.35, p < 0.001). In RA patients with high ACPA titers (≥ 200 U/mL), sTIM-3 was not correlated with ESR or MMP-3. Whereas, sTIM-3 was significantly correlated with ESR and MMP-3 in RA patients with low ACPA titers (< 200 U/mL). Conclusions Serum sTIM-3 was increased in RA patients, and it was associated with proinflammatory markers and disease activity in RA patients under a particular ACPA status. Our data suggest that circulating sTIM-3 may be a useful biomarker for the determination of disease activity in RA patients.

Sign in / Sign up

Export Citation Format

Share Document