Abstract:
:A novel, constitutively expressed and secreted interleukin 18 (IL18) binding protein (IL18BP) neutralises IL18. IL18BP shares many characteristics with soluble cytokine receptors of the IL1 family in that the protein exhibits specificity for IL18, belongs to the immunoglobulin-like class of receptors and has limited amino acid sequences with those of the IL1 receptor type II. However, unlike soluble cytokine receptors, IL18BP does not have a transmembrane domain and hence is not anchored to the cell membrane. IL18BP is a secreted protein and not cleaved from the cell surface. IL18BP is naturally occurring and was isolated from the urine of healthy subjects. Because IL18 is an important inducer of interferon gamma (IFNgamma), IL18BP suppresses the production of IFNgamma resulting in reduced T-helper type 1 immune responses. There are four human and two mouse isoforms-resulting from mRNA splicing and found in various cDNA libraries. Each of these IL18BP isoforms have been expressed, purified and assessed for binding and neutralisation of IL18 biological activities. Two human IL18BP isoforms exhibited the greatest affinity for IL18 with a rapid on-rate, a slow off-rate and a dissociation constant (kDa) of 399 pM. The two other isoforms with an incomplete immunoglobulin domain were unable to neutralise IL18. The two human isoforms that possess a complete immunoglobulin domain, neutralise >95% IL18 at a molar excess of two. Molecular modelling identified a large mixed electrostatic and hydrophobic binding site in the immunoglobulin domain of IL18BP, which could account for its high affinity binding to the ligand. These high affinity forms may be ideally suited for blocking IL18 in human disease. It is likely that preferential secretion of high affinity functional and non-functional isoforms of IL18BP affect the immune response and the outcome of disease.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Dinarello CAdoi
10.1136/ard.59.suppl_1.i17subject
Has Abstractpub_date
2000-11-01 00:00:00pages
i17-20eissn
0003-4967issn
1468-2060journal_volume
59 Suppl 1pub_type
杂志文章,评审abstract:OBJECTIVES:Evidence suggests that doxycycline might have disease-modifying properties in osteoarthritis. However, the clinically relevant question as to whether doxycycline also modifies symptoms in knee osteoarthritis is unanswered. The objective of this study was to investigate the effectiveness of doxycycline on pai...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/ard.2010.147967
更新日期:2011-07-01 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:OBJECTIVE:To confirm and extend the immunopathological evidence of effects of infliximab on the synovium in active spondyloarthropathy. METHODS:Synovial biopsies obtained in patients with spondyloarthropathy at baseline and week 12 were stained and scored by two independent observers. Two study populations were evalua...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/ard.2003.018549
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVE:The first genome-wide association study (GWAS) of systemic sclerosis (SSc) demonstrated three non-major histocompatibility complex (MHC) susceptibility loci. The goal of this study was to investigate the impact of these gene variants on survival and severity of interstitial lung disease (ILD) in SSc. METHODS...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2011-200901
更新日期:2012-07-01 00:00:00
abstract:OBJECTIVE:To determine the circulating serum concentrations of nerve growth factor (NGF) and compare them with indices of disease activity in juvenile chronic arthritis. METHODS:NGF concentrations were evaluated with a two site immunoenzymatic assay (ELISA), in 17 children with systemic, 39 with polyarticular, and 24 ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.55.10.745
更新日期:1996-10-01 00:00:00
abstract::A nephelometric assay of concanavalin-A binding of serum acute phase proteins (con-A binding) has been used in cross-sectional and sequential studies of disease activity in rheumatoid arthritis (RA). Con-A binding correlated well with blood viscosity, C-reactive protein, and other individual acute phase reactants in p...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.41.2.133
更新日期:1982-04-01 00:00:00
abstract::Evidence is presented that a single injection of bacterial antigen in oil into a footpad of rats of 5 strains induced different clinical forms of adjuvant disease in the individual rat strains. Rats were injected with 300 micrograms heat-killed Mycobacterium tuberculosis in 50 microliters paraffin. Inflammatory lesion...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.41.5.538
更新日期:1982-10-01 00:00:00
abstract::We have compared the distribution of histocompatibility antigens of 22 Turkish and 14 British patients with Behçet's disease with those of their respective controls. There was a strong association of B5, specifically its Bw51 split, with the disease. A modest increase in the incidence of HLA B27 was noted in British p...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.39.4.344
更新日期:1980-08-01 00:00:00
abstract::Pulmonary hypertension in systemic lupus erythematosus (SLE) is rare in the absence of parenchymal lung disease. We report such a case, which was complicated by the subsequent development of a left recurrent laryngeal nerve palsy, and in which there was a strong family history of SLE. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.46.3.246
更新日期:1987-03-01 00:00:00
abstract:BACKGROUND:Bone erosion is a common manifestation of chronic tophaceous gout. OBJECTIVES:To investigate the effects of monosodium urate monohydrate (MSU) crystals on osteoblast viability and function. METHODS:The MTT assay and flow cytometry were used to assess osteoblast cell viability in the MC3T3-E1 and ST2 osteob...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.144774
更新日期:2011-09-01 00:00:00
abstract:OBJECTIVE:To assess the usefulness of high resolution computed tomography (HRCT) of the lungs in patients with rheumatoid arthritis (RA) with and without respiratory symptoms. PATIENTS AND METHODS:Eighty eight RA patients with a mean duration of disease 12 (SD 8) years were evaluated. Eleven patients were excluded bec...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.10.815
更新日期:1995-10-01 00:00:00
abstract:OBJECTIVE:We sought to determine histologic and gene expression features of clinical improvement in early diffuse cutaneous systemic sclerosis (dcSSc; scleroderma). METHODS:Fifty-eight forearm biopsies were evaluated from 26 individuals with dcSSc in two clinical trials. Histologic/immunophenotypic assessments of glob...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2020-217840
更新日期:2021-02-01 00:00:00
abstract::Feverfew, reputed by folklore to be effective in arthritis, has in vitro properties that could be beneficial in the control of inflammatory disease. Forty one female patients with symptomatic rheumatoid arthritis received either dried chopped feverfew (70-86 mg) or placebo capsules once daily for six weeks. Allocation...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/ard.48.7.547
更新日期:1989-07-01 00:00:00
abstract:OBJECTIVE:To carry out a critical appraisal of the literature in an attempt to assess the current value of synovial fluid (SF) analysis in the diagnosis of joint disease. METHODS:A literature search was undertaken using the Medline, Biomed, Bids, Pubmed, and Embase electronic databases using the keywords: synovial flu...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.61.6.493
更新日期:2002-06-01 00:00:00
abstract:OBJECTIVES:To define pulmonary involvement on high resolution computed tomography (HRCT) of the thorax in lifelong non-smoking rheumatoid arthritis patients and to relate the results to pulmonary function, bronchial reactivity, and a variety of clinical and serological factors. METHODS:Twenty lifelong non-smoking RA p...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.4.308
更新日期:1995-04-01 00:00:00
abstract:OBJECTIVES:To characterise and quantify the CD4+ CD25+ T cell population in patients with systemic lupus erythematosus (SLE) and to detect the possible influence of treatments and clinical manifestations. METHODS:Characterisation of CD25(low) and CD25(high) CD4+ T cells from healthy controls and from patients with SLE...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.049924
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVES:To evaluate the rate of tuberculosis (TB) in biologic users for rheumatic diseases in South Africa, the effectiveness of our latent TB infection (LTBI) programme, risk factors and outcome. METHODS:TB cases were collected from the South African Biologics Registry (SABIO), rheumatologists and pharmaceutical c...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2019-216128
更新日期:2020-02-01 00:00:00
abstract::In a multicentre study patients with rheumatoid arthritis judged by prevailing criteria to be suitable for synovectomy of the knee or metacarpophalangeal (MCP) joints were randomly allocated to one of two groups. One group had the operation, the other was observed without operation from a notional corresponding date. ...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1975-10-01 00:00:00
abstract::Pain in the neck and upper limb is common and contributes considerably to absence from work due to sickness. Evidence suggest that prolonged abnormal posture and repetition contribute to such conditions. Psychosocial risk factors may also play a part in the aetiology of upper limb disorders. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,收录出版,评审
doi:10.1136/ard.2003.020016
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVE:To investigate quantitatively the mRNA expression levels of YKL-40, an established marker of rheumatoid and osteoarthritic cartilage degeneration in synovial fluid and serum, and a closely related molecule YKL-39, in articular chondrocytes. METHODS:cDNA array and online quantitative polymerase chain reaction...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.62.10.995
更新日期:2003-10-01 00:00:00
abstract:OBJECTIVE:To evaluate the efficacy and safety of adding sulfasalazine to leflunomide treatment compared with switching to sulfasalazine alone in patients with RA with an inadequate response to leflunomide monotherapy. METHODS:Patients with active RA ((DAS28) >3.2) who were enrolled in the first open label phase of the...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1136/ard.2003.016709
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVE:Regulatory T cells (Tregs) with the plasticity of producing proinflammatory cytokine IL-17 have been demonstrated under normal and pathogenic conditions. However, it remains unclear whether IL-17-producing Tregs lose their suppressive functions because of their plasticity toward Th17 in autoimmunity. The aim ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204228
更新日期:2015-06-01 00:00:00
abstract::Gout and classical rheumatoid arthritis rarely coexist. We report a patient with strong evidence for both these diseases. Possible reasons for the negative correlation between these diseases are summarised. One hypothesis suggests inhibition of surface activity of monosodium urate crystals (MSU) by binding of rheumato...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.6.384
更新日期:1985-06-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to assess the value of power Doppler ultrasound (PDUS) in combination with routine management in a cohort of patients with very early inflammatory arthritis (IA). METHODS:50 patients with < or =12 weeks of inflammatory symptoms with or without signs had clinical, laboratory and ima...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.106658
更新日期:2010-02-01 00:00:00
abstract:OBJECTIVE:To assess the value of advanced imaging techniques in the detection of hand osteoarthritis (OA) and hand OA progression. METHODS:PubMed/Medline and Embase were searched until April 2012 for studies on imaging of hand OA that presented quantitative data on validity, reliability or responsiveness. Articles pre...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2012-202515
更新日期:2014-02-01 00:00:00
abstract::Ten patients (8 female, 2 male) with systemic lupus erythematosus (SLE) were entered into an open trial with the anabolic steroid 19-nortestosterone (19-nor). Their clinical condition did not improve, nor were significant changes observed in the majority of laboratory data. However, overall the platelet count rose, an...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.42.2.155
更新日期:1983-04-01 00:00:00
abstract:OBJECTIVES:Systemic immunological processes are profoundly shaped by the micro-environments where antigen recognition occurs. Identifying molecular signatures distinctive of such processes is pivotal to understand pathogenic immune responses and manipulate them for therapeutic purposes. Unfortunately, direct investigat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206226
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVE:Spondyloarthritis is a group of articular disorders sharing a genetic background. Polymorphisms in the IL-1 gene cluster have previously been associated with ankylosing spondylitis (AS), a subset of spondyloarthritis. This study examined the association between several of these polymorphisms and the whole spo...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200439
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVES:Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA). METHODS:Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200096
更新日期:2012-01-01 00:00:00
abstract::A new method is described for separating free 35SO4-- from 35SO4 labelled proteoglycans synthesised by rabbit articular chondrocytes cultured in the presence of excess 35SO4--. The procedure uses the low solubility product of barium sulphate to remove, by precipitation, free 35SO4-- from culture medium. Optimum recove...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.48.5.372
更新日期:1989-05-01 00:00:00