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

scholarly journals Molecular Characterisation of the Synovial Fluid Microbiome in Rheumatoid Arthritis Patients and Healthy Control Subjects

2018 ◽  
Author(s):  
Dargham Bayan Mohsen Hammad ◽  
Veranja Liyanapathirana ◽  
Daniel Paul Tonge
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
16S Rrna ◽  
Disease Status ◽  
16S Rrna Genes ◽  
Rrna Genes ◽  
Internal Transcribed Spacer Region ◽  
Control Subjects ◽  
Healthy Control ◽  
Fungal Dna

AbstractThe colonisation of specific body sites in contact with the external environment by microorganisms is both well-described and universally accepted, whereas, the existence of microbial evidence in other “classically sterile” locations including the blood, synovial space, and lungs, is a relatively new concept. Increasingly, a role for the microbiome in disease is being considered, and it is therefore necessary to increase our understanding of these. To date, little data support the existence of a “synovial fluid microbiome”.MethodsThe presence and identity of bacterial and fungal DNA in the synovial fluid of rheumatoid arthritis (RA) patients and healthy control subjects was investigated through amplification and sequencing of the bacterial 16S rRNA gene and fungal internal transcribed spacer region 2 respectively. Synovial fluid concentrations of the cytokines IL-6, IL-17A, IL22 and IL-23 were determined by ELISA.ResultsBacterial 16S rRNA genes were detected in 87.5% RA patients, and all healthy control subjects. At the phylum level, the microbiome was predominated byProteobacteria(Control = 83.5%, RA = 79.3%) andFirmicutes(Control = 16.1%, RA = 20.3%), and to a much lesser extent,Actinobacteria(Control = 0.2%, RA = 0.3%) andBacteroidetes(Control = 0.1%, RA = 0.1%). Fungal DNA was identified in 75% RA samples, and 88.8% healthy controls. At the phylum level, synovial fluid was predominated by members of the Basidiomycota (Control = 53.9%, RA = 46.9%) and Ascomycota (Control = 35.1%, RA = 50.8%) phyla. Statistical analysis revealed key taxa that were differentially present or abundant dependent on disease status.ConclusionsThis study reports the presence of a synovial fluid microbiome, and determines that this is modulated by disease status (RA) as are other classical microbiome niches.

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 Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

2016 ◽  
Vol 100 (4) ◽  
pp. 823-833 ◽  
Author(s):  
Jayesh M. Pandya ◽  
Anna-Carin Lundell ◽  
Magnus Hallström ◽  
Kerstin Andersson ◽  
Inger Nordström ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
T Helper ◽  
Control Subjects ◽  
Healthy Control

The Lung Microbiome Differs in Asymptomatic Subjects at Elevated Risk of Future Rheumatoid Arthritis Compared with Healthy Control Subjects

2014 ◽  
Vol 11 (Supplement 1) ◽  
pp. S74-S74 ◽  
Author(s):  
M. Kristen Demoruelle ◽  
Jill M. Norris ◽  
V. Michael Holers ◽  
J. Kirk Harris ◽  
Kevin D. Deane
Keyword(s):  
Rheumatoid Arthritis ◽  
Elevated Risk ◽  
Control Subjects ◽  
Lung Microbiome ◽  
Healthy Control ◽  
Asymptomatic Subjects

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.

Urinary Glycosaminoglycan Excretion in Rheumatic Diseases

1992 ◽  
Vol 38 (6) ◽  
pp. 841-846 ◽  
Author(s):  
V Kéry ◽  
M Orlovská ◽  
M Stancíková ◽  
M Risko ◽  
D Zlnay
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Decision Analysis ◽  
Alcian Blue ◽  
Rheumatic Diseases ◽  
Clinical Decision ◽  
Control Subjects ◽  
Significant Difference ◽  
Healthy Control ◽  
Urine Specimens

Abstract We used Alcian Blue (AB) and dimethylmethylene blue (DMB) methods to measure glycosaminoglycan (GAG) excretion in the first morning urine specimens of patients with osteoarthritis (OA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA) in different stages of disease. By the AB method, urinary GAG excretion in patients with RA was not different from healthy control subjects. However, the DMB method showed significant differences (in milligrams of GAG per gram of creatinine) for OA (median 25.4, range 14.3-44.0, P less than 0.01, n = 23) and RA patients (median 33.0; range 10.0-147.6; P less than 0.001, n = 63) in comparison with unaffected individuals (median 20.2; range 8.9-41.4, n = 38). We noted a significant difference in urinary GAG excretion between RA and OA patients (P less than 0.01) and between RA and AS (P less than 0.01) patients. The DMB method was further investigated by clinical decision analysis. The DMB method is simple and rapid and may be useful in diagnosing RA by distinguishing between RA and OA or AS.

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.

Enhancement of Platelet Sensitivity to ADP-Aggregation by Isometric Exercise in Arteriosclerotic Patients and its Prevention

1977 ◽  
Vol 37 (02) ◽  
pp. 329-338 ◽  
Author(s):  
Tadahiro Sano ◽  
Takeshi Motomiya ◽  
Hiroh Yamazaki ◽  
Takio Shimamoto
Keyword(s):  
Cyclic Amp ◽  
Mechanical Stress ◽  
Optical Density ◽  
Platelet Function ◽  
Isometric Exercise ◽  
Phosphodiesterase Inhibitor ◽  
New Method ◽  
Platelet Aggregability ◽  
Control Subjects ◽  
Healthy Control

SummaryA new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points:1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment.2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positive significant correlations between the values obtained by these three methods.3. It was proved to be highly reproducible and is thought to be useful clinically.By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement of platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.

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