scholarly journals AB0106 THE SERUM N-ACETYLGLUCOSAMINE CONCENTRATIONS IN RHEUMATOID ARTHRITIS PATIENTS ARE ASSOCIATED WITH JOINT DESTRUCTION AND RELATED METABOLISM MORE THAN INFLAMMATORY CONDITION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1352.2-1352
Author(s):  
S. Tsuboi ◽  
T. Matsumoto ◽  
Y. Kagawa
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Cartilage ◽  
Negative Correlation ◽  
High Speed ◽  
Wrist Joint ◽  
Cartilage Damage ◽  
Joint Destruction ◽  
Basal Metabolism ◽  
Joint Disease ◽  
Precipitation Method

Background:In rheumatoid arthritis (RA) patients, synovitis causes severe articular cartilage damage. N-acetylglucosamine (NAc-Glc) is a component of gluglucosaminoglycans (GAG) such as hyaluronic acid (HA) and keratan sulfate (KS), heparan sulfate (HS). NAc-Glc concentration in plasma is thought to reflect the balance between biosynthesis and destruction of articular cartilage, however, few studies had examined the relationship between plasma NAc-Glc conncentration and RA activity.Objectives:NAc-Glc concentrations in RA patients were measured, and association with clinical indicators was assessed.Methods:A cross-sectional study was carried out including 60 RA cases. Using N-acetylglucosamine-d3 as standard, the serum of subjects were deproteinized by protein precipitation method with acetonitrile, then concentration of NAc-Glc was measured with high-speed liquid chromatography mass spectrometer (LC-MS / MS). Clinical evaluation items: basic metabolism, presence or absence of exercise habit, Larsen score of knee and wrist joint, therapeutic agents (csDMARDs, biologics and PSL), DAS28, CRP, MMP-3, modified HAQ score (mHAQ). Statically analyzed by Spearman non parametric test.Results:The age of 60 RA cases was 59.7±16.4 years, and the duration of the disease was 10.4±8.7 years. Biologics were used in 29 cases (TNF inhibitors in 16 cases, IL-6 inhibitors in 4 cases, Abatacept in 9 cases), MTX in 32 cases, and prednisolone in 15 cases.Plasma NAc-Glc concentration was 113±41 (ng/dl), DAS28CRP was 3.04±1.2, and mHAQ was 0.863±891. Plasma NAc-Glc concentration showed positive correlation with age (correlation coefficient 0.644), knee joint destruction (0.425), HAQ score (0.340), BUN (0.412), and RF (0.287). Plasma NAc-Glc concentrations also negatively correlated with eGFR (-0.597), MTX use (-0.389), basal metabolism (-0.313), and sex difference (-0.272). There was no correlation between plasma NAc-Glc concentration and body weight, BMI, DAS28, CRP, MMP-3, NTX, serum creatinine, hand joint disease, and transaminase.In this study, plasma NAc-Glc concentration had increased with age, and had have a negative correlation with basal metabolism. Considering these results, it is unlikely that NAc-Glc is released into plasma as a metabolite of synthesis promotion. Further, since NAc-Glc had a negative correlation (-0.389) with MTX as a folic acid inhibitor, it was supposed to be affected by protein synthesis reduction. Because no correlation between NAc-Glc and inflammation or bone metabolism markers was observed, NAc-Glc may represent removal of GAG from the cell membrane (shedding).In previous GAGs studies, in RA patients, HA, KS, CRP, DAS28, was very associated with arthritis, such as MMP-3.The concentration of NAc-Glc in plasma was more relevant to dysfunctions such as destruction and HAQ due to arthritis such as HAQ than inflammatory indicators such as DAS28, MMP-3 and CRP. It is appearing in the plasma by destruction by shedding, as an index to see the joint destruction, it was presumed to be a better indicator than the GAGs. It was also thought that there is a possibility that MTX affects cartilage substrate metabolism.Conclusion:Serum NAc-Glc concentration in rheumatoid arthritis patients may represent cartilage metabolism and joint destruction.References:[1]Y.Matsuura. et al.Ann.Rheum.Dis. 2018;77: 1219-1225[2]T D Spector.et al. Ann.Rheum.Dis. 1992;51: 1134-1137Disclosure of Interests:None declared

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

scholarly journals The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4968
Author(s):  
Samuel García-Arellano ◽  
Luis Alexis Hernández-Palma ◽  
Sergio Cerpa-Cruz ◽  
Gabriela Athziri Sánchez-Zuno ◽  
Melva Guadalupe Herrera-Godina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Joint Destruction ◽  
Study Groups ◽  
Joint Disease ◽  
The Novel ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Dysregulation ◽  
New Evidence

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.

scholarly journals Fibroblast Like Synovial Cell Subsets in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Søren Lomholt ◽  
Morten A. Nielsen ◽  
Maithri P. Aspari ◽  
Peter B. Jørgensen ◽  
Adam P. Croft ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cartilage Damage ◽  
Joint Destruction ◽  
Human Leukocyte ◽  
Synovial Cell ◽  
Joint Inflammation ◽  
Nuclear Factor Κb ◽  
Sequencing Studies ◽  
Sublining Layer ◽  
Lymphoid Structures

Fibroblasts like synoviocytes (FLS) play several significant roles in rheumatoid arthritis (RA) pathophysiology. This chapter will describe known roles of FLS in disease initiation, joint inflammation, disease persistence and joint destruction. It will describe the newly characterized subsets of FLS based on single cell RNA sequencing studies, and their association to specific aspects of the disease. Finally, we will discuss the future of targeting FLS in the treatment of RA. The FLS in the synovial lining layer are identified by surface complement decay-accelerating factor (CD55) along with lubricin and metallopeptidase expression. Pathological activation of this lining layer subset result in bone and cartilage damage in mice. FLS of the sublining layer are often characterized by THY1 expression, but recent studies have highlighted a heterogeneity where several distinct subsets are identified by additional markers. Sublining FLS expressing human leukocyte antigen-DRA (HLA-DRA) produce C-X-C motif chemokine 12 (CXCL12) and receptor activator of nuclear factor-κB ligand (RANKL) and seems to constitute a pro-inflammatory subset that is associated with inflammation and tertiary lymphoid structures. Another subset of FLS characterized by CD34 expression may discriminate a common progenitor fibroblast subset. Taken together, studies isolating and characterizing gene expression in synovial FLS report both associations of unknown importance and markers that may impose protective or destructive features. This supports evidence of FLS as active players in RA pathology capable of cellular recruitment, local cellular crosstalk and promotion of joint destruction. These discoveries may serve as an atlas for synovial activation in RA and have identified several potential fibroblast markers for the development of targeted treatment.

scholarly journals The Micro-Immunotherapy Medicine 2LARTH® Reduces Inflammation and Symptoms of Rheumatoid Arthritis In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ilaria Floris ◽  
Víctor García-González ◽  
Belen Palomares ◽  
Kurt Appel ◽  
Beatrice Lejeune
Keyword(s):  
Rheumatoid Arthritis ◽  
Histological Analysis ◽  
Pure Water ◽  
Joint Destruction ◽  
Clinical Signs ◽  
Clinical Score ◽  
Type Ii Collagen ◽  
Joint Disease ◽  
Paw Edema

Background. Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damages as well as pain and disability. In order to prevent disease progression, reduce pain, and major symptoms of RA, one good strategy consists in targeting proinflammatory cytokines that have the key role in the vicious circle of synovial inflammation and pain. The micro-immunotherapy medicine (MIM) 2LARTH® targets cytokines involved in inflammation. Aim. The aim of the study is to evaluate the effect of the MIM compared to vehicle in an in vivo model of RA, induced in mice after immunization with articular bovine type II collagen. Methods. Vehicle and MIM were dissolved in pure water (1 capsule in 100 ml) and 100 µl was given by gavage daily for 14 days. To evaluate the severity of arthritis, wrist and ankle thickness was determined, paw edema was measured, and a clinical score from 0 to 4 was established. Furthermore, histological analysis was performed. To evaluate systemic inflammation, circulating levels of IL-1β and TNF-α were measured by ELISA. Results. Ankle thickness was found to be significantly reduced in MIM-treated mice compared to vehicle-treated mice (P<0.05) and compared to untreated me (P<0.01). Paw edema was reduced, as well as clinical score attributed to MIM-treated mice in comparison with vehicle-treated mice and untreated CIA mice (P<0.01). In line with these results, histological analysis confirmed that MIM reduced inflammation and joint destruction in comparison to controls. No significant changes were found in plasmatic IL-1β levels between CIA and controls, while the levels of TNF-α significantly increased in the CIA group, and were lowered in MIM-treated mice (P<0.05 vs. vehicle and vs. CIA). Conclusion. The results indicate that the tested medicine reduces inflammation, histological, and clinical signs of RA in a CIA model.

scholarly journals Elevated APE1/Ref-1 Levels of Synovial Fluids in Patients with Rheumatoid Arthritis: Reflection of Disease Activity

2021 ◽  
Vol 10 (22) ◽  
pp. 5324
Author(s):  
In Seol Yoo ◽  
Yu-Ran Lee ◽  
Seong Wook Kang ◽  
Jinhyun Kim ◽  
Hee-Kyoung Joo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Joint Inflammation ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Control ◽  
The Relationship

There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and synovial fluid (SF) were collected from 46 patients with RA, 45 patients with osteoarthritis (OA), and 30 healthy control (HC) patients. The concentration of APE1/Ref-1 in serum or SF was measured using the sandwich enzyme-linked immunosorbent assay (ELISA). The disease activity in RA patients was measured using the 28-joint disease activity score (DAS28). The serum APE1/Ref-1 levels in RA patients were significantly increased compared to HC and OA patients (0.44 ± 0.39 ng/mL for RA group vs. 0.19 ± 0.14 ng/mL for HC group, p < 0.05 and vs. 0.19 ± 0.11 ng/mL for OA group, p < 0.05). Likewise, the APE1/Ref-1 levels of SF in RA patients were also significantly increased compared to OA patients (0.68 ± 0.30 ng/mL for RA group vs. 0.31 ± 0.12 ng/mL for OA group, p < 0.001). The APE1/Ref-1 concentration in SF of RA patients was positively correlated with DAS28. Thus, APE1/Ref-1 may reflect the joint inflammation and be associated with disease activity in RA.

scholarly journals Arthritis and the role of endogenous glucocorticoids

Bone Research ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Eugenie Macfarlane ◽  
Markus J. Seibel ◽  
Hong Zhou
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Current Evidence ◽  
Inflammatory Microenvironment ◽  
Glucocorticoid Signaling ◽  
Anti Inflammatory ◽  
Fibroblast Like Synoviocytes

Abstract Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.

Rheumatoid Arthritis and Fibromyalgia: A Frequent Unrelated Association Complicating Disease Management

2009 ◽  
Vol 36 (1) ◽  
pp. 58-62 ◽  
Author(s):  
FABIENNE COURY ◽  
ARNAUD ROSSAT ◽  
ALEXANDRE TEBIB ◽  
MARIE-CLAUDE LETROUBLON ◽  
ANNE GAGNARD ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Joint Destruction ◽  
Constant Factor ◽  
Joint Disease ◽  
Psychosocial Characteristics ◽  
Inappropriate Treatment ◽  
The Relationship ◽  
Worse Prognosis

ObjectiveTo assess the value of the 28-joint Disease Activity Score (DAS28) in evaluating disease activity in rheumatoid arthritis (RA) associated with fibromyalgia (FM). In this situation, because of the weight of the subjective measures included in the DAS28 equation, the patient’s status may be overestimated, leading to inappropriate treatment. We analyze the relationship between RA and FM and discuss whether the association is random or a marker of poor prognosis.MethodsA questionnaire, developed when biologic therapies were introduced, was administered and the results analyzed in a consecutive, female outpatient population including 105 patients with RA, 49 with RA and FM (RAF), and 28 with FM. Psychosocial characteristics, disease presentation, and radiographic joint destruction evaluation were compared in the 3 populations.ResultsThe presentation of RA was the same in patients with RA and RAF, but the 2 populations differed by socioprofessional characteristics, significantly higher disease activity in patients with RAF, and significantly more severe joint destruction in patients with RA. The RAF group was similar to the FM control population in socioprofessional and some physical characteristics. Regression analysis using the DAS28 measures differed significantly in the weight allowed to 28-joint counts for pain and swelling, but the constant factor was higher in patients with RAF.ConclusionDAS28 overestimated objective RA severity in patients who also had FM. The association between RA and FM does not appear to be a marker of worse prognosis, but rather a fortuitous association between the 2 diseases and one that may afford these patients some protection against joint destruction.

scholarly journals The Natural History of Haemophilic Arthritis

1977 ◽  
Author(s):  
J.E. Handelsman ◽  
A.L. Lurie ◽  
J.J. Rippey ◽  
R.R. Hill ◽  
M.B.E. Sweet ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Biochemical Analysis ◽  
Weight Bearing ◽  
Cartilage Damage ◽  
Joint Destruction ◽  
Knee Joints ◽  
Round Cell Infiltration ◽  
Infiltrating Cells ◽  
Cell Layers ◽  
History Of

Surgical exploration of eight chronically afflicted haemophilic knee joints in patients aged 6 to 31 years, has revealed a pattern of progressive arthropathy.Significant synovial changes occurred very early. Cellular overgrowth produced thickening, convolution and increased vascularity. Haemosiderin was deposited heavily in all cell layers. Fibrosis ultimately contracted the synovium.Chronic inflammation produced epiphyseal overgrowth. Initially, articular cartilage changes resembled chondromalacia, but fissuring soon occurred and ultimately cartilage was totally lost over central weight-bearing areas and in the intercondylar region. Anomalies of matrix, chondrocyte aggregation and death, and subchondral round cell infiltration were features. Haemosiderin staining was sparse, occurring only in some chondrocytes and infiltrating cells.Biochemical analysis of articular cartilage biopsies revealed a severe depletion of glycosaminoglycans. There was no biochemical evidence of a reaction of repair.Articular cartilage damage occurred mainly between the ages of 6 and 10 years. This evidence suggests that early surgical synovectomy may arrest the process that produces progressive joint destruction.

T2 Mapping as a New Method for Quantitative Assessment of Cartilage Damage in Rheumatoid Arthritis

2019 ◽  
Vol 47 (6) ◽  
pp. 820-825 ◽  
Author(s):  
Nina Renner ◽  
Arnd Kleyer ◽  
Gerhard Krönke ◽  
David Simon ◽  
Stefan Söllner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Cartilage ◽  
Disease Activity ◽  
Disease Duration ◽  
T2 Mapping ◽  
Cartilage Damage ◽  
Relaxation Times ◽  
T2 Relaxation ◽  
Hand Joints ◽  
Magnetic Resonance Imaging Mri

Objective.Rheumatoid arthritis (RA) is associated with damage of the articular cartilage and the periarticular bone. While imaging of bone damage has substantially improved in recent years, direct imaging of the articular cartilage of the hand joints in patients with RA is still challenging. The study used T2 mapping of the finger joints to assess cartilage damage in RA.Methods.Magnetic resonance imaging (MRI) at 3 Tesla was done in 30 patients with RA, and T2 relaxation times visualizing alteration in the collagen network and hydration of articular cartilage were mapped in 6 cartilage regions of the metacarpophalangeal (MCP) joints 2 and 3. Values were related to autoantibody status [anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF)], disease duration, and disease activity as well as sex and age of the patients.Results.T2 relaxation times could be reliably measured in the 6 regions of the MCP joints. Significantly higher relaxation times indicating more advanced cartilage alterations were observed in the metacarpal heads of ACPA-positive (p = 0.001–0.010) and RF-positive patients (p = 0.013–0.025) as well as those with longer disease duration (> 3 yrs; p = 0.028–0.043). Current disease activity, sex, and age did not influence T2 relaxation times.Conclusion.These data show that cartilage damage can be localized and quantified in the hand joints of patients with RA by T2 mapping. Further, ACPA and RF positivity as well as disease duration appear to be the crucial factors influencing cartilage damage.

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