Abstract:
OBJECTIVES:While new treatments for rheumatoid arthritis (RA) have markedly improved disease control by targeting immune/inflammatory pathways, current treatments rarely induce remission, underscoring the need for therapies that target other aspects of the disease. Little is known about the regulation of disease severity and joint damage, which are major predictors of disease outcome, and might be better or complementary targets for therapy. In this study, we aimed to discover and characterise a new arthritis severity gene. METHODS:An unbiased and phenotype-driven strategy including studies of unique congenic rat strains was used to identify new arthritis severity and joint damage genes. Fibroblast-like synoviocytes (FLS) from rats and patients with RA expressing or not Huntingtin-interacting protein 1 (HIP1) were studied for invasiveness, morphology and cell signalling. HIP1 knockout mice were used in in vivo confirmatory studies. Paired t-test was used. RESULTS:DNA sequencing and subcongenic strains studied in pristane-induced arthritis identified a new amino acid changing functional variant in HIP1. HIP1 was required for the increased invasiveness of FLS from arthritic rats and from patients with RA. Knocking down HIP1 expression reduced receptor tyrosine kinase-mediated responses in RA FLS, including RAC1 activation, affecting actin cytoskeleton and cell morphology and interfering with the formation of lamellipodia, consistent with reduced invasiveness. HIP1 knockout mice were protected in KRN serum-induced arthritis and developed milder disease. CONCLUSION:HIP1 is a new arthritis severity gene and a potential novel prognostic biomarker and target for therapy in RA.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Laragione T,Brenner M,Lahiri A,Gao E,Harris C,Gulko PSdoi
10.1136/annrheumdis-2018-213498subject
Has Abstractpub_date
2018-11-01 00:00:00pages
1627-1635issue
11eissn
0003-4967issn
1468-2060pii
annrheumdis-2018-213498journal_volume
77pub_type
杂志文章abstract:BACKGROUND:Vascular damage is a key pathological process in systemic sclerosis (SSc) and accounts for significant disease-related morbidity. To determine the clinical burden of severe digital vasculopathy (SDV), we have reviewed hospital-based treatment for this important complication of SSc in a large single centre co...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.072686
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVES:Systemic sclerosis (SSc) is a rare disease requiring multicentre collaboration to reveal comprehensive details of disease-related causes for morbidity and mortality. METHODS:The European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) group initiated a database to prospectively ga...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2011-200742
更新日期:2012-08-01 00:00:00
abstract::A careful selection of 19 patients fitting the classical description of polymyalgia rheumatica have been examined by arthroscopy and thoroughly screened and followed up to exclude rheumatoid arthritis and other disease processes. Synovitis of the shoulder joint has been observed through the arthroscope in 17 and synov...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.42.3.311
更新日期:1983-06-01 00:00:00
abstract:OBJECTIVE:To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS). PATIENTS AND METHODS:We include 1045 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological chara...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206418
更新日期:2016-02-01 00:00:00
abstract::The microfocal x-ray unit, a new type of x-ray machine characterised by an extremely small x-ray source, enables great detail to be recorded in the projection radiographs owing to the high object magnification and resolution obtained with this system. Microfocal radiographic examinations were carried out on the wrists...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.2.160
更新日期:1984-04-01 00:00:00
abstract:OBJECTIVES:To determine the accuracy of ultrasonography (US) for bone erosion detection in different areas of rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints with multislice CT as the reference method. Second, to establish the necessary bone volume loss on CT for US to reliably detect it as an erosion, and f...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/annrheumdis-2011-201114
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVE:To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA). METHODS:Patients with active early RA (disease duration of ≤12 months) were randomly assigned ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/annrheumdis-2012-201612
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVES:MRI scoring systems for hand osteoarthritis (HOA) are currently not available. The present work proposes the Oslo HOA MRI (OHOA-MRI) score and examines the intrareader and inter-reader reliability. METHODS:Relevant HOA features were included in the initial version of the OHOA-MRI score after literature revi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.144527
更新日期:2011-06-01 00:00:00
abstract::This paper presents the second update of the Assessment in SpondyloArthritis international Society (ASAS) consensus statement on the use of anti-tumour necrosis factor (anti-TNF) agents in patients with axial spondyloarthritis (SpA). A major change from the previous recommendations is that patients fulfilling the ASAS...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章
doi:10.1136/ard.2011.151563
更新日期:2011-06-01 00:00:00
abstract:OBJECTIVES:To identify new susceptibility loci for Behçet's disease (BD), we performed a genome-wide association study (GWAS) using DNA pooling. METHODS:Two replicate pools of 292 Iranian BD cases and of 294 age- and sex-matched controls were allelotyped in quadruplicate on the Affymetrix Genome-Wide Human SNP Array 6...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204475
更新日期:2015-03-01 00:00:00
abstract:OBJECTIVES:Over 50% of patients with rheumatoid arthritis (RA) harbour a variety of anti-modified protein antibodies (AMPA) against different post-translationally modified (PTM) proteins, including anti-carbamylated protein (anti-CarP) antibodies. At present, it is unknown how AMPA are generated and how autoreactive B ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2016-210772
更新日期:2017-08-01 00:00:00
abstract:OBJECTIVES:In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo. METHODS:Patien...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2017-212504
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVE:Notch signalling pathways are critical for angiogenesis and endothelial cell (EC) fate; however the mechanisms regulating these processes in the inflamed joint remain to be elucidated. Here, we examine whether Notch signalling mediates vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2)-induce...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-201978
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVE:To investigate the prevalence and clinical significance of carotid artery intima-media thickness (IMT) in patients with primary antiphospholipid syndrome (APS). METHODS:28 patients with primary APS with at least a five year follow up, and 28 healthy subjects, matched by age and sex, were included in the stud...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.62.7.607
更新日期:2003-07-01 00:00:00
abstract::We report two cases of osteomyelitis secondary to staphylococcal septicaemia, presenting with large sterile effusions in adjacent joints. In both cases the clinical features were suggestive of septic arthritis. Multiple joints were involved in each patient. Initial radiographs showed no abnormalities. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.4.607
更新日期:1984-08-01 00:00:00
abstract:OBJECTIVE:To investigate the rate of incident diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) and the impact of disease-modifying antirheumatic drug (DMARD) and statin treatments. METHODS:We studied patients with RA and ≥1 year participation in the National Data Bank for Rheumatic Diseases without ba...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2016-209954
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:A prolonged symptom or disease duration at treatment initiation is associated with unfavourable outcomes in rheumatoid arthritis (RA). It is unknown whether this relation is linear, referring to a common 'the-earlier-the-better principle', or whether a transient time frame in which the disease is more suscep...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206047
更新日期:2015-05-01 00:00:00
abstract::IgM rheumatoid factor (RF) was measured in the sera of 48 rheumatoid patients and of 48 age and sex-matched normal controls by the Rose-Waaler and latex agglutination tests, a rate nephelometer, and an enzyme-linked immunosorbent assay (ELISA). Good correlation was obtained between all assays. The rate nephelometer as...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.1.13
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVE:To localise and characterise follicular dendritic cells (FDC) present in autoimmune lesions of primary Sjögren syndrome. METHODS:Cryostat sections of labial salivary glands from 15 patients with primary Sjögren syndrome were examined by an indirect immunoperoxidase technique and monoclonal antibodies to a pa...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.56.2.140
更新日期:1997-02-01 00:00:00
abstract:OBJECTIVES:The relationship between radiographic evidence of osteoarthritis and knee pain has been weak. This may be because features that best discriminate knees with pain have not been included in analyses. We tested the correlation between knee pain and radiographic features taking into account both image analysis f...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2018-213492
更新日期:2018-11-01 00:00:00
abstract:OBJECTIVE:Although genome-wide association studies (GWAS) have identified approximately 100 loci for rheumatoid arthritis (RA), the disease mechanisms are not completely understood. We evaluated the pathogenesis of RA by focusing on rare coding variants. METHODS:The coding regions of 98 candidate genes identified by G...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2019-215062
更新日期:2019-08-01 00:00:00
abstract:OBJECTIVE:To determine whether mild variation in acetabular depth (AD) and shape is a risk factor for osteoarthritis (OA) of the hip. METHODS:The unaffected contralateral hip of patients with unilateral hip OA was compared with hips of asymptomatic controls without hip OA, derived from the Nottingham Genetics Osteoart...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.127076
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND:Primary Sjögren's syndrome (pSS) is characterised by a chronic inflammation of exocrine glands. Salivary gland infiltrates, however, do not correlate well with disease symptoms, and a primary role for the salivary gland parenchyma in disease development has been suggested. Specifically, dysfunction of exocri...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2010.138966
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:Previous studies have reported an interaction between ever cigarette smoking and the presence of the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype and rheumatoid arthritis (RA) risk. To address the effect of dosage, a case-control study nested within two prospective cohorts to determine the...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2008.102962
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVE:To analyse tender and swollen joint counts in three cohorts of patients with rheumatoid arthritis (RA), with a focus on the proportions of patients who had fewer than 6-12 tender or swollen joints, as possible evidence based information toward more generalisable inclusion criteria for current and future RA cl...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.044131
更新日期:2006-07-01 00:00:00
abstract:BACKGROUND:Population mean changes from clinical trials are difficult to apply to individuals in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. METHODS:The numbers of patients with pain relief over baseline (> or =15%, > or =30%, > or =50%, > or ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析
doi:10.1136/ard.2009.107805
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Patients with rheumatoid arthritis (RA) have an increased risk of certain solid cancers, in particular lung cancer, compared to the general population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may further enhance this risk. OBJECTIVES:To compare the risk of solid cancer in patients with...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204851
更新日期:2015-06-01 00:00:00
abstract::The rapid introduction of immunotherapies for cancer-targeting immunological checkpoints has led to a new class of toxicities that appear to be of autoimmune and or autoinflammatory origin. These disorders are now referred to as immune-related adverse events (irAEs) and pose considerable challenges to patient care in ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2017-212061
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVES:Advanced imaging studies have demonstrated that urate deposition in periarticular structures, such as tendons, is common in gout. The aim of this study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on tenocyte viability and function. METHODS:The histological appearance of ten...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204657
更新日期:2014-09-01 00:00:00
abstract::The phenomenon of increased spontaneous incorporation of 3H-thymidine (3H-TdR) into peripheral blood mononuclear cells in rheumatoid arthritis (RA) has been investigated. The activity was found to be short lived and affected less than 1% of cells. Using a Percoll density gradient we identified two populations of activ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.5.703
更新日期:1984-10-01 00:00:00