Abstract:
INTRODUCTION:Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA. METHODS:1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied. RESULTS:We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P = 2.35x10-4). This variant was also significant after Bonferroni correction. CONCLUSIONS:These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Knevel R,de Rooy DP,Saxne T,Lindqvist E,Leijsma MK,Daha NA,Koeleman BP,Tsonaka R,Houwing-Duistermaat JJ,Schonkeren JJ,Toes RE,Huizinga TW,Brouwer E,Wilson AG,van der Helm-van Mil AHdoi
10.1186/ar4558subject
Has Abstractpub_date
2014-05-07 00:00:00pages
R108issue
3eissn
1478-6354issn
1478-6362pii
ar4558journal_volume
16pub_type
杂志文章abstract:BACKGROUND:The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZB x NZW) F1 murine lupus model. METHODS:Female NZB/W F1 mice (11 weeks old) were treated daily with 25 or 50 mg/kg oral spironolactone or vehicle. Proteinuria...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2353
更新日期:2008-01-01 00:00:00
abstract::Irreversible destruction of joint structures is a major feature of osteoarthritis and rheumatoid arthritis. Fibrillar collagens in bone, cartilage and other soft tissues are critical for optimal joint form and function. Several approaches can be used to ascertain the role of collagenases, matrix metalloproteinases, in...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar600
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Differences in the expression of variants across ethnic groups in the systemic lupus erythematosus (SLE) patients have been well documented. However, the genetic architecture in the Thai population has not been thoroughly examined. In this study, we carried out genome-wide association study (GWAS) in the Tha...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02276-y
更新日期:2020-08-08 00:00:00
abstract:INTRODUCTION:We previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used to target anti-inflammatory therapeutics specifically to inflamed arthritic joints. The objective of the present study was to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4613
更新日期:2014-07-16 00:00:00
abstract:BACKGROUND:Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and, consequently, enhances cell migration. Desp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02204-0
更新日期:2020-05-15 00:00:00
abstract:BACKGROUND:Pepsin agglutinators, discovered over 50 years ago, have been recently referred to as anti-hinge antibodies (AHAs) because of their reaction with the IgG hinge epitope. AHAs have different reactivity for each hinge epitope generated by each protease that cleaves the hinge region at different sites. Moreover,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02251-7
更新日期:2020-06-26 00:00:00
abstract:INTRODUCTION:miR-146a is one of the first identified miRNAs expressed differentially in osteoarthritis (OA) cartilage. However, the role it plays in OA pathogenesis is not clear. The aim of this study is to identify a molecular target of miR-146a, thereby elucidating its function in chondrocytes during OA pathogenesis....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3798
更新日期:2012-04-16 00:00:00
abstract:BACKGROUND:The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to ex...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1332-y
更新日期:2017-06-02 00:00:00
abstract:INTRODUCTION:Our objectives were to examine mononuclear cell gene expression profiles in patients with systemic lupus erythematosus (SLE) and healthy controls and to compare subsets with and without atherosclerosis to determine which genes' expression is related to atherosclerosis in SLE. METHODS:Monocytes were obtain...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4609
更新日期:2014-07-10 00:00:00
abstract:BACKGROUND:We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4+ T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1278-0
更新日期:2017-04-11 00:00:00
abstract:BACKGROUND:Some abnormalities in nailfold videocapillaroscopy (NVC), such as the presence of micro-haemorrhages (MHEs), micro-thromboses (MTs), giant capillaries (GCs) and reduction in the number of capillaries (nCs), suggest a disease activity (DA) phase in systemic sclerosis (SSc). In a previous paper, we showed that...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-017-1354-5
更新日期:2017-06-13 00:00:00
abstract::In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1737
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. METHODS:Fine n...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1594-z
更新日期:2018-06-08 00:00:00
abstract:INTRODUCTION:Data from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-α therapy in patients with ankylosing spondylitis (AS) are scarce. This is the first report on continuous treatment with the TNFα fusion protein etanercept over seven years (y). METHODS:Overall, 26 patients...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4244
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:To aim was to investigate the additional value of incorporating the de Vlam cervical facet joint score in the modified ankylosing spondylitis (AS) spine score (mSASSS) for the evaluation of spinal radiographic outcome in AS. METHOD:Baseline and 4-year radiographs from 98 consecutive patients from the Gronin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1285-1
更新日期:2017-04-26 00:00:00
abstract:BACKGROUND:Interleukin-17A (IL-17A) plays a pathogenic role in several rheumatic diseases including spondyloarthritis and, paradoxically, has been described to both promote and protect from bone formation. We therefore examined the effects of IL-17A on osteoblast differentiation in vitro and on periosteal bone formatio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0998-x
更新日期:2016-05-10 00:00:00
abstract:INTRODUCTION:The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. METHODS:Serum resistin levels were determin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3836
更新日期:2012-05-11 00:00:00
abstract::Historically, the osteoblast has been considered the master cell in the control of osteoclast development and, therefore, bone resorption. Now the interactions between cells of the immune system and bone cells have redefined our thinking on the regulation of bone resorption. Moreover, the crosstalk between these cell ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2141
更新日期:2007-01-01 00:00:00
abstract::The article by Seror et al. in Arthritis Research & Therapy reports data from the 15 French patients in the open-label BELISS (Efficacy and Safety of Belimumab in Subjects With Primary Sjögren's Syndrome, NCT01160666) study of belimumab in primary Sjögren's syndrome. The study identifies that higher baseline levels of...
journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/s13075-015-0878-9
更新日期:2015-12-07 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a me...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1122-y
更新日期:2016-10-06 00:00:00
abstract:BACKGROUND:In recent decades, low-level laser therapy (LLLT) has been widely used to relieve pain caused by different musculoskeletal disorders. Though widely used, its reported therapeutic outcomes are varied and conflicting. Results similarly conflict regarding its usage in patients with nonspecific chronic low back ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s13075-015-0882-0
更新日期:2015-12-15 00:00:00
abstract:INTRODUCTION:Soluble immune aggregates bearing intact Fc fragments are effective treatment for a variety of autoimmune disorders in mice. The better to understand the mechanisms by which Fc-bearing immune complexes suppress autoimmunity, and to develop a platform for clinical translation, we created a series of fully r...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4024
更新日期:2012-08-20 00:00:00
abstract:INTRODUCTION:Though remission is currently a treatment goal in patients with rheumatoid arthritis (RA), the number of patients who achieve and sustain remission in daily practice is still small. It is suggested that early remission will be associated with sustainability of remission. The aim was to study the associatio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3027
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accurac...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4383
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVES:To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). METHODS:All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02231-x
更新日期:2020-06-15 00:00:00
abstract:INTRODUCTION:Rituximab (RTX) therapy of rheumatoid arthritis (RA) exhibits enhanced effectiveness in seropositive patients. Using patient sera, we tested if this improved efficacy was associated with enhanced RTX mediated complement-dependent cytotoxicity (RTX-CDC). METHODS:We developed an in vitro assay for RTX-CDC u...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4152
更新日期:2013-01-25 00:00:00
abstract:INTRODUCTION:Tumor necrosis factor (TNF) antagonists reduce the signs and symptoms of spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Our objective was to evaluate the effectiveness and safety of adalimumab, 40 mg every other week, for patients with AS or PsA and prior treatmen...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar3054
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To cl...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4345
更新日期:2013-10-24 00:00:00
abstract:INTRODUCTION:Cell therapy is a rapidly growing area of research for the treatment of osteoarthritis (OA). This work is aimed to investigate the efficacy of intra-articular adipose-derived stromal cell (ASC) injection in the healing process on cartilage, synovial membrane and menisci in an experimental rabbit model. ME...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4156
更新日期:2013-01-29 00:00:00
abstract:BACKGROUND:Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. There is a need for bio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1040-z
更新日期:2016-06-16 00:00:00