scholarly journals Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 53
Author(s):  
Theoharris Frangos ◽  
Wolfgang Maret
Keyword(s):  
Rheumatoid Arthritis ◽  
Metal Ions ◽  
Joint Destruction ◽  
Joint Damage ◽  
Redox Balance ◽  
Essential Metal ◽  
Arthritic Disease ◽  
Human Proteins ◽  
Inflammatory State ◽  
The Many

Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory articular conditions with different aetiology, but both result in joint damage. The nutritionally essential metal zinc (Zn2+) and the non-essential metal cadmium (Cd2+) have roles in these arthritic diseases as effectors of the immune system, inflammation, and metabolism. Despite both metal ions being redox-inert in biology, they affect the redox balance. It has been known for decades that zinc decreases in the blood of RA patients. It is largely unknown, however, whether this change is only a manifestation of an acute phase response in inflammation or relates to altered availability of zinc in tissues and consequently requires changes of zinc in the diet. As a cofactor in over 3000 human proteins and as a signaling ion, zinc affects many pathways relevant for arthritic disease. How it affects the diseases is not just a question of zinc status, but also an issue of mutations in the many proteins that maintain cellular zinc homoeostasis, such as zinc transporters of the ZIP (Zrt-/Irt-like protein) and ZnT families and metallothioneins, and the multiple pathways that change the expression of these proteins. Cadmium interferes with zinc’s functions and there is increased uptake under zinc deficiency. Remarkably, cadmium exposure through inhalation is now recognized in the activation of macrophages to a pro-inflammatory state and suggested as a trigger of a specific form of nodular RA. Here, we discuss how these metal ions participate in the genetic, metabolic, and environmental factors that lead to joint destruction. We conclude that both metal ions should be monitored routinely in arthritic disease and that there is untapped potential for prognosis and treatment.

scholarly journals Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

2021 ◽  
Vol 10 (6) ◽  
pp. 1241
Author(s):  
Yoshiya Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Kinase Inhibitors ◽  
Joint Destruction ◽  
Joint Damage ◽  
Nuclear Factor Κb ◽  
Cartilage Destruction ◽  
Janus Kinase ◽  
Systemic Autoimmune Disease ◽  
And Cartilage

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

scholarly journals Assessment of synovitis to predict bone erosions in rheumatoid arthritis

2012 ◽  
Vol 4 (4) ◽  
pp. 235-244 ◽  
Author(s):  
Serena Bugatti ◽  
Antonio Manzo ◽  
Roberto Caporali ◽  
Carlomaurizio Montecucco
Keyword(s):  
Rheumatoid Arthritis ◽  
Progressive Disease ◽  
Imaging Techniques ◽  
Joint Destruction ◽  
Joint Damage ◽  
Assessment Tools ◽  
Rapid Progression ◽  
Radiographic Outcomes ◽  
Clinical Measures ◽  
Synovial Tissue Analysis

Although rheumatoid arthritis (RA) is traditionally considered as the prototype of destructive arthritis, the course of the disease varies considerably, with some patients experiencing more rapid progression of joint damage and disability than others. Given the increasing availability of treatment targets and options, timely recognition of individual’s outcomes could allow therapeutic allocation according to personalized benefit–risk profiles. Research efforts are thus increasingly focused at discovering predictive markers that could identify patients with aggressive, rapidly progressive disease and poor prognosis. As joint destruction in RA is the result of the cumulative burden of inflammation, variables reflecting the severity of synovitis and its persistence over time might refine our ability to build early prognostic algorithms. The goal of this article is to review the clinical implications of the assessment of synovitis in relation to radiographic outcomes. Traditional and novel assessment tools will be discussed, including clinical measures, imaging techniques and tissue biomarkers. Achievements in the field of synovial tissue analysis and peripheral blood biomarkers of synovitis represent only the first steps of ongoing progress, which still need to be integrated into the phenotypic heterogeneity of RA.

scholarly journals Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis

2009 ◽  
Vol 69 (3) ◽  
pp. 567-570 ◽  
Author(s):  
Hans Ulrich Scherer ◽  
Michael P M van der Linden ◽  
Fina A S Kurreeman ◽  
Gerrie Stoeken-Rijsbergen ◽  
Saskia le Cessie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Joint Destruction ◽  
Joint Damage ◽  
Negative Regulator ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Factor Α

BackgroundTwo novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor α-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-κB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA.ObjectiveTo analyse the effect of the 6q23 region on the rate of joint destruction.MethodsFive single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years.ResultsTwo polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment.ConclusionsThese data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.

Genetic Factors for the Severity of ACPA-negative Rheumatoid Arthritis in 2 Cohorts of Early Disease: A Genome-wide Study

2015 ◽  
Vol 42 (8) ◽  
pp. 1383-1391 ◽  
Author(s):  
Diederik P.C. de Rooy ◽  
Roula Tsonaka ◽  
Maria L.E. Andersson ◽  
Kristina Forslind ◽  
Alexandra Zhernakova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Noncoding Rna ◽  
Genetic Factors ◽  
Phase 1 ◽  
Joint Destruction ◽  
Joint Damage ◽  
Phase 2 ◽  
Early Ra ◽  
Genome Wide ◽  
A Genome

Objective.Rheumatoid arthritis (RA) that is negative for anticitrullinated protein antibodies (ACPA) is a subentity of RA, characterized by less severe disease. At the individual level, however, considerable differences in the severity of joint destruction occur. We performed a study on genetic factors underlying the differences in joint destruction in ACPA-negative patients.Methods.A genome-wide association study was done with 262 ACPA-negative patients with early RA included in the Leiden Early Arthritis Clinic and related to radiographic joint destruction over 7 years. Significant single-nucleotide polymorphisms (SNP) were evaluated for association with progression of radiographic joint destruction in 253 ACPA-negative patients with early RA included in the Better Anti-Rheumatic Farmaco Therapy (BARFOT) study. According to the Bonferroni correction of the number of tested SNP, the threshold for significance was p < 2 × 10−7 in phase 1 and 0.0045 in phase 2. In both cohorts, joint destruction was measured by Sharp/van der Heijde method with good reproducibility.Results.Thirty-three SNP associated with severity of joint destruction (p < 2 × 10−7) in phase 1. In phase 2, rs2833522 (p = 0.0049) showed borderline significance. A combined analysis of both the Leiden and BARFOT datasets of rs2833522 confirmed this association with joint destruction (p = 3.57 × 10−9); the minor allele (A) associated with more severe damage (for instance, after 7 yrs followup, patients carrying AA had 1.22 times more joint damage compared to patients carrying AG and 1.50 times more joint damage than patients carrying GG). In silico analysis using the ENCODE and Ensembl databases showed presence of H3K4me3 histone mark, transcription factors, and long noncoding RNA in the region of rs2833522, an intergenic SNP located between HUNK and SCAF4.Conclusion.Rs2833522 might be associated with the severity of joint destruction in ACPA-negative RA.

scholarly journals Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?

2015 ◽  
Vol 42 (7) ◽  
pp. 1131-1140 ◽  
Author(s):  
Ian C. Scott ◽  
Frühling Rijsdijk ◽  
Jemma Walker ◽  
Jelmar Quist ◽  
Sarah L. Spain ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Severity ◽  
Genetic Risk Score ◽  
Joint Destruction ◽  
Health Assessment ◽  
Joint Damage ◽  
Joint Disease ◽  
Nucleotide Polymorphisms ◽  
Radiological Progression ◽  
Weighted Genetic Risk Score

Objective.Genetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA.Methods.We evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants — 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions — for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models.Results.HLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP — rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) — associated with HAQ scores over 6–24 months.Conclusion.HLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.

scholarly journals 161 Cross Sectional Study of Pharmacological Management of Rheumatoid Arthritis in Patients over the age of 70

2019 ◽  
Vol 48 (Supplement_3) ◽  
pp. iii17-iii65
Author(s):  
Catriona Reddin ◽  
Maria Costello ◽  
Bernadette Lynch
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Joint Destruction ◽  
Joint Damage ◽  
Joint Disease ◽  
Older Population ◽  
Record System ◽  
Cross Sectional ◽  
Therapeutic Benefits ◽  
Conventional Dmards

Abstract Background Rheumatoid arthritis (RA) is a common inflammatory joint disease. It can lead to joint destruction resulting in joint deformity, functional impairment and reduced mobility. With a growing older population, prevalence of RA is increasing and due to the associated morbidity it is essential to prioritise disease control. Conventional treatment of RA has comprised of disease modifying anti rheumatic drugs (DMARDs) along with analgesia and corticosteroids. Recently, the development of biologics has revolutionised management of inflammatory arthritis. We now strive for tighter control to prevent joint damage and preserve function. However, studies have shown that uptake of biologic medications in the older population has been slower than their younger counterparts. (1) Methods Our departmental electronic record system, Cellma, was interrogated for patients aged 70 and over with a diagnosis of RA. Deceased patients were excluded. The current medication list was reviewed using the online rheumatology outpatient system. Results A total of 514 patients over the age of 70 were identified with a diagnosis of RA [(67% (n=343) female, 33% (n=171) male)], 24.5% (n=126) were on biologic therapy, 13% (n=68) patients were on a single DMARD in combination with a biologic, 42% (n=217) of patients were on a single conventional DMARD alone and 9.7% (n=50) were on analgesia alone. Conclusion The management of RA in the older population poses its own challenges but this should not prohibit the thoughtful use of newer agents. Awareness of the therapeutic potential and associated adverse events is necessary for maximizing therapeutic benefits while minimizing adverse effects from conventional DMARDs and biologic therapies.

Calprotectin (a major S100 leucocyte protein) predicts 10-year radiographic progression in patients with rheumatoid arthritis

2008 ◽  
Vol 69 (01) ◽  
pp. 150-154 ◽  
Author(s):  
H Berner Hammer ◽  
S Ødegård ◽  
S W Syversen ◽  
R Landewé ◽  
D van der Heijde ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Independent Predictor ◽  
Joint Destruction ◽  
Joint Damage ◽  
Radiographic Damage ◽  
Erosive Disease ◽  
Reactive Protein ◽  
Sharp Score ◽  
Markers Of Inflammation ◽  
Articular Damage

Background:Plasma levels of calprotectin, a major S100 leucocyte protein, are cross-sectionally associated with clinical and laboratory markers of inflammation and with radiographic damage in rheumatoid arthritis (RA). High amounts of calprotectin are found in synovial fluid from patients with RA.Objective:To examine whether calprotectin might be an independent predictor of joint destruction over time.Methods:124 patients with RA were assessed at baseline and after 10 years with inflammatory markers (calprotectin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)), serological variables (antibodies to cyclic citrullinated peptide (anti-CCP), IgA rheumatoid factor (RF) and IgM RF) and radiographic and clinical assessments of joint damage (hand radiographs and Rheumatoid Arthritis Articular Damage (RAAD) score). Progression of radiographic damage was assessed according to the van der Heijde modified Sharp score.Results:At both examinations the highest calprotectin levels were found in patients positive for anti-CCP, IgA and IgM RF. Calprotectin had moderate to good correlations with inflammatory and serological markers (r = 0.41–0.67). Patients with normal baseline calprotectin levels had a lower degree of joint damage. High univariate associations were found between baseline calprotectin levels and progression in the Sharp score as well as the RAAD score. Baseline calprotectin was independently associated with progression in the Sharp score and with the RAAD score in multiple linear regression analyses, including baseline levels of CRP, ESR, anti-CCP in addition to demographic variables.Conclusion:Calprotectin was an independent predictor of clinical and radiographic joint damage after 10 years. These findings support the proposal that calprotectin may be a prognostic biomarker for erosive disease in patients with RA.

scholarly journals Electrochemical Immunosensor for Simultaneous Determination of Emerging Autoimmune Disease Biomarkers in Human Serum

2021 ◽  
Vol 3 (1) ◽  
pp. 24
Author(s):  
Esther Sánchez-Tirado ◽  
Sara Guerrero ◽  
Araceli González-Cortés ◽  
Lourdes Agüí ◽  
Paloma Yáñez-Sedeño ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Serum ◽  
Simultaneous Determination ◽  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Joint Destruction ◽  
Joint Damage ◽  
Necrosis Factor Alpha ◽  
Extracellular Matrix Components

Rheumatoid arthritis is an autoimmune disorder characterized by persistent erosive synovitis, systemic inflammation and the presence of autoantibodies, which play an important role in inducing inflammation and joint damage, releasing pro-inflammatory cytokines from monocytes and macrophages [1,2]. Likewise, neutrophil activating protein-2 (CXCL7) is a platelet-derived growth factor belonging to the CXC chemokine subfamily, which is expressed in serum, synovial fluid and synovial tissue of patients developing rheumatoid arthritis during the first twelve weeks, being useful to reflect local pathological changes [3]. Besides, matrix metalloproteinase-3 (MMP-3), which is induced by inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α) in rheumatoid synovium, degrades several extracellular matrix components of cartilage and plays central roles in rheumatoid joint destruction [4]. Therefore, monitoring serum CXCL7 and MMP-3 levels is useful for predicting the disease activity in rheumatoid arthritis. In this work, the construction and analytical performance of a dual electrochemical platform for the simultaneous determination of CXCL7 and MMP-3 is described. After the optimization of experimental variables involved in the preparation and implementation of the biosensor, the analytical usefulness of the developed configuration was demonstrated by its application to the determination of these biomarkers in serum samples from healthy individuals and patients with rheumatoid arthritis. To carry out the simultaneous determination of CXCL7 and MMP3 in human serum, just a fifty-fold sample dilution in PBS of pH 7.4 was required. In addition, the results obtained using the dual immunosensor were compared with those provided by the respective ELISA immunoassays, yielding no significant differences between the two methods. It is important to highlight that reagents consumption, four times smaller using the dual immunosensor than that required in the ELISA protocol, and an assay time of 2 h 50 min versus almost 5 h, counted in both cases after incubation of the capture antibody, are advantageous features of the dual immunosensor [5].

scholarly journals Elevated serum granzyme B levels are associated with disease activity and joint damage in patients with rheumatoid arthritis

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096295
Author(s):  
Junjie Qiao ◽  
Meng Zhou ◽  
Zheng Li ◽  
Jie Ren ◽  
Guanghan Gao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Features ◽  
Granzyme B ◽  
Joint Destruction ◽  
Elevated Serum ◽  
Joint Damage ◽  
Laboratory Evaluation ◽  
Potential Applications ◽  
Joint Erosion

Objectives Little is known about the roles of granzyme B in rheumatoid arthritis (RA). We aimed to evaluate the serum level of granzyme B in patients with RA and determine relationships with clinical features and joint destruction of RA. Methods We enrolled 100 patients with RA, 50 patients with osteoarthritis (OA), and 50 healthy controls (HC). Granzyme B serum concentrations were measured by ELISA; we then analyzed associations between granzyme B levels, clinical features, and joint destruction by calculating Sharp scores and disease activity as measured by Disease Activity Score-28 based on erythrocyte sedimentation rate (DAS28-ESR) in patients with RA. Results Compared with HC and patients with OA, serum granzyme B levels in patients with RA were remarkably elevated. Serum granzyme B levels did not differ between patients with OA and HC. Granzyme B levels correlated with ESR, rheumatoid factor, swollen joint counts, joint erosion scores, total Sharp scores, and DAS28-ESR. Moreover, patients with RA with high disease activity had higher granzyme B levels. Conclusions Serum granzyme B levels were elevated significantly in patients with RA and correlated positively with disease activity and joint destruction. Serum granzyme B may have potential applications in laboratory evaluation of patients with RA.

scholarly journals Treatment strategy for patients with rheumatoid arthritis

2020 ◽  
Vol 63 (7) ◽  
pp. 422-430
Author(s):  
Soo-Kyung Cho ◽  
Yoon-Kyoung Sung
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Targeted Therapies ◽  
Functional Disability ◽  
Joint Destruction ◽  
Joint Damage ◽  
Chronic Inflammatory Disease ◽  
Biologic Dmards

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the joints, causing joint destruction, functional disability, and reduced quality of life in patients. The aim of RA treatment is to decrease the inflammation, prevent joint damage, and improve patientsʼ quality of life while minimizing progression of the disease. Both early detection and intervention with disease-modifying anti-rheumatic drugs (DMARDs) have been reported to improve therapeutic outcomes. Treatment with DMARDs should be started immediately after the diagnosis is established, with methotrexate as the best initial drug of choice. Disease activity should be regularly monitored. Targeted therapies can be considered in patients with persistent active disease despite methotrexate therapy. Remission or low disease activity is the preferred treatment target. There are two major classes of DMARDs: conventional synthetic DMARDs and the targeted therapies specific to pro-inflammatory cytokines including biologic DMARDs and small molecule inhibitors. Recently, the importance of shared decision making, in which patients and clinicians make decisions together, and education of the patient has been emphasized in the treatment strategies of RA. This review summarizes the effectiveness and safety of the DMARDs currently available for RA treatment. Recommendations for RA management would also be discussed in this article.

Sign in / Sign up

Export Citation Format

Share Document