Abstract:
OBJECTIVES:To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. METHODS:An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×106, 3×106 or 10×106 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood. RESULTS:There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×106 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high. CONCLUSION:IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×106 tolDC but no systemic clinical or immunomodulatory effects were detectable. TRIAL REGISTRATION NUMBER:NCT01352858.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Bell GM,Anderson AE,Diboll J,Reece R,Eltherington O,Harry RA,Fouweather T,MacDonald C,Chadwick T,McColl E,Dunn J,Dickinson AM,Hilkens CM,Isaacs JDdoi
10.1136/annrheumdis-2015-208456subject
Has Abstractpub_date
2017-01-01 00:00:00pages
227-234issue
1eissn
0003-4967issn
1468-2060pii
annrheumdis-2015-208456journal_volume
76pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Persistent fibroblast activation initiated by transforming growth factor β (TGF-β) is a fundamental event in the pathogenesis of systemic sclerosis, and its pharmacological inhibition represents a potential therapeutic strategy. The nuclear receptor, peroxisome proliferator-activated receptor γ (PPAR-γ), exe...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-202716
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Entheseal fibrocartilage (EF) derangement is hypothesised to be pivotal to the pathogenesis of spondyloarthritis. Ultrasound is useful for visualisation of the enthesis but its role in EF visualisation is uncertain. This work aimed to demonstrate face and content validity of ultrasound for EF visualisation b...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.127175
更新日期:2010-12-01 00:00:00
abstract:OBJECTIVES:To compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs). METHODS:Adults aged 50-80 years (n=59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2011-200970
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVES:In systemic sclerosis (SSc), vascular involvement is characterised by vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR) system disturbances. Neuropilin-1 (NRP1), a receptor for both class-3 semaphorins (Sema3s) and VEGF-A, is required for optimal VEGF-A/VEGFR-2 signalling. Here, we investigat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-207483
更新日期:2016-08-01 00:00:00
abstract:OBJECTIVE:To determine the influence of TAP1 and TAP2 alleles in northwestern Colombian patients with systemic lupus erythematosus (SLE). METHODS:Unselected patients with SLE (n=140) and controls (n=120) matched for sex, age, and ethnicity were analysed. Clinical manifestations, clinical activity, and severity of dise...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.62.4.363
更新日期:2003-04-01 00:00:00
abstract::It has been proposed that the process of hypoxic-reperfusion injury contributes to the persistence of synovitis in the inflamed human joint. The generation of pathological, exercise induced, intra-articular pressure leading to occlusion of the synovial microcirculation is central to this mechanism. However, acute trau...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.50.12.917
更新日期:1991-12-01 00:00:00
abstract:OBJECTIVE:Knee osteoarthritis commonly requires joint replacement, substantially reduces quality of life and increases healthcare utilisation and costs. This study aimed to identify whether quantitative measures of articular cartilage structure predict knee replacement, and to establish their utility as outcomes in cli...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2011-201164
更新日期:2013-05-01 00:00:00
abstract::A case of pachydermoperiostosis characterised by the presence of finger clubbing, periostosis, sweating of hands and feet is described. Modifications of capillaroscopic pattern and of arteriovenous anastomoses are reported. The periungual border and finger tip tissue showed diffuse endothelial hyperplasia, hyalinosis,...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.48.3.240
更新日期:1989-03-01 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:BACKGROUND:Matrix metalloproteinase (MMP)1, interleukin(IL)6 and vitamin D receptor (VDR) have been implicated in the biological cascade of events initiated by particulate wear debris and bacterial infection, resulting in periprosthetic bone loss around loosened total hip replacements (THRs). The individual responses t...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.062018
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND:Hand exercises are recommended for patients with hand osteoarthritis (HOA), though evidence for their effect is conflicting. OBJECTIVE:To evaluate, in a randomised controlled trial, the effect of HOA information plus home-based hand exercises (exercise group) compared with information only (control group) i...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2013-204808
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) worldwide. The disease is caused by mutations in the MEFV gene encoding the inflammasome sensor Pyrin. Clinical diagnosis of FMF is complicated by overlap in symptoms with other diseases, and interpre...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2019-216701
更新日期:2020-07-01 00:00:00
abstract::The adherent cells remaining after short-term culture of synovial fluid and synovial membrane cells from rheumatoid and non-rheumatoid patients were examined for the presence of a productive virus infection and for various viral antigens. Labelling was carried out with 3H-thymidine and 3H-uridine followed by sucrose d...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.39.2.159
更新日期:1980-04-01 00:00:00
abstract:OBJECTIVES:To estimate the incidence of postinfectious joint complaints after Campylobacter jejuni/coli enteritis compared with enteritis caused by enterotoxigenic E coli (ETEC). To compare gastrointestinal symptoms, antibiotic treatment, and antibody levels among patients with and without joint symptoms. METHOD:Quest...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.5.448
更新日期:2002-05-01 00:00:00
abstract::The serological diagnosis of juvenile rheumatoid arthritis (JRA) is difficult, with only 7-10% of patients 19S IgM rheumatoid factor positive. About 60-70% of patients are positive for hidden 19S IgM rheumatoid factor, but this test requires serum separation and is not available in most laboratories. Antiperinuclear f...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.3.350
更新日期:1992-03-01 00:00:00
abstract::In the World Health Organisation's supplementary classification of the consequences of disease a distinction is made between impairments, such as are related to the site and nature of joint involvement, and any disabilities in everyday activities to which these may give rise. This paper considers the application of th...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.4.563
更新日期:1984-08-01 00:00:00
abstract::We studied the course of adjuvant arthritis in rats by measuring clinical, biochemical, and histological parameters on day 36 after induction (representing the secondary reaction) and on day 171, which is at the stage of permanent deformity. The effect of SR 41319, a new diphosphonate, was evaluated on days 36 and 171...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.45.1.67
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVE:To determine whether abnormalities in the function of the autonomic nervous system are associated with oral and ocular dryness in rheumatoid arthritis. METHODS:Pupillography was done using an infrared light reflection method (IRIS) to measure both parasympathetic function (constriction latency and the latenc...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.55.9.612
更新日期:1996-09-01 00:00:00
abstract:BACKGROUND:Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of inflixima...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.057406
更新日期:2007-02-01 00:00:00
abstract::The effect of transforming growth factor beta (TGF beta) on proteoglycan synthesis and degradation in anatomically intact articular cartilage of murine patellae was studied. Exogenously added TGF beta up to a concentration of 200 pmol/l had no effect on proteoglycan synthesis in intact articular cartilage. Neutralisat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.5.643
更新日期:1992-05-01 00:00:00
abstract:OBJECTIVE:To elucidate factors involved in the arthritogenicity of bacterial cell walls. METHODS:For characterisation of an arthritogenic Eubacterium aerofaciens cell wall, peptidoglycan-polysaccharide (PG-PS) polymers were isolated by removing cell wall associated proteins (CWPs), PG and PS moieties were separated, a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.3.269
更新日期:2001-03-01 00:00:00
abstract::Peritoneal serositis is not a widely recognised aspect of systemic lupus erythematosus (SLE). Indeed, ascites in SLE is said to occur only when complicated by the nephrotic syndrome, congestive cardiac failure, or hepatic cirrhosis. We describe two patients who developed ascites that could be attributed to none of the...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.11.778
更新日期:1985-11-01 00:00:00
abstract:BACKGROUND:The PTPN22 gene has been widely confirmed as a susceptibility gene for rheumatoid arthritis (RA) in populations of Northern European descent. The aim of the current study was to explore the role of variants spanning the PTPN22 gene in determining susceptibility to and outcome of inflammatory polyarthritis (I...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.071894
更新日期:2008-02-01 00:00:00
abstract::OBJECTIVE: To examine the risk of major cardiovascular disease associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a large 'real-world' contemporary rheumatoid arthritis (RA) cohort. METHODS: A longitudinal cohort study was conducted with use of Danish nationwide individual-level registry data on inpat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-203137
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:High rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling. OBJECTIVES:To assess the influence of maternal serum cytokine levels on birth weig...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2012-202539
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Preliminary clinical criteria based on age, inflammation, and immobility have been proposed to identify which patients with rheumatoid arthritis (RA) should be examined by dual energy x ray absorptiometry (DXA) to diagnose osteoporosis. The three item criteria have not been evaluated in male patients with RA...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.12.1085
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:Several inflammatory conditions are associated with an increased risk of lymphoma. The specific features of inflammation that mediate this risk are unknown. There are few studies on whether ankylosing spondylitis increases the risk of lymphoma. Besides inflammation-lymphoma aetiology, information on risk of ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.047514
更新日期:2006-09-01 00:00:00
abstract:OBJECTIVES:Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (-168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarctio...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.059428
更新日期:2007-03-01 00:00:00
abstract:OBJECTIVE:To investigate the first-ever incidence of acute myocardial infarction and stroke in a community based RA cohort compared with the general population. METHODS:The RA cohort consisted of all patients in a local RA register in Malmö, Sweden (n = 1022). The patients were recruited from private and hospital base...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.018101
更新日期:2004-08-01 00:00:00
abstract::The effects of fasting for 7 days were investigated in 13 patients with rheumatoid arthritis (RA) in comparison with a control regimen in a cross-over trial. The effects of fasting on clinical performance and blood neutrophil functions were studied. During fasting, with a mean weight loss of 5.1 kg, clinical inflammat...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.42.1.45
更新日期:1983-02-01 00:00:00