Abstract:
BACKGROUND:Anti-citrullinated protein antibodies (ACPAs) are the hallmark of rheumatoid arthritis (RA). Protein citrullination is believed to drive autoantigen selection in RA. Nonetheless, several autoantigens in RA are targeted as native (unmodified) proteins. Here, the study of hnRNP A2/B1 (RA33) provides a framework to understand the humoral response to native and citrullinated autoantigens in RA. METHODS:RA synovial fluid (SF) cells were analysed by immunoblotting and mass spectrometry. RA33 was cloned from RASF cells and splice variants expressed as recombinant proteins. Antibodies against native and citrullinated RA33 were characterised by ELISA, immunoblotting and immunoprecipitation. RESULTS:RA33 is citrullinated in the rheumatoid joint and targeted either as a citrullinated or native protein in distinct patient subsets with RA. A novel splice variant (hnRNP B1b) previously associated with disease initiation in experimental arthritis was identified in the RA joint and acts as the major target of the anti-RA33 response. Antibodies exclusively targeting citrullinated RA33 were positively associated with disease duration and erosive disease. In contrast, anti-(native) RA33 antibodies were detected almost exclusively in early RA and identified patients with low radiographic erosion scores. Finally, a unique subset of double-reactive patients demonstrated intermediate severity, but rapid disease progression, suggesting a transitional disease phase in the evolution of an anti-native protein antibody to ACPA response in RA. CONCLUSIONS:These data suggest that native and citrullinated proteins targeted by autoantibodies in RA may be part of a single antibody system and challenge the paradigm of citrullination as the unifying principle underlying loss of tolerance in RA.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Konig MF,Giles JT,Nigrovic PA,Andrade Fdoi
10.1136/annrheumdis-2015-208529subject
Has Abstractpub_date
2016-11-01 00:00:00pages
2022-2028issue
11eissn
0003-4967issn
1468-2060pii
annrheumdis-2015-208529journal_volume
75pub_type
杂志文章abstract::Leishmaniasis is an intracellular protozoan infection that can lead to cutaneous, mucocutaneous, visceral or systemic manifestations depending on the parasite species and virulence and on the host immune response. It is endemic in countries of Europe (Mediterranean basin), Asia, Africa, Central and South America, but ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2011-200596
更新日期:2012-04-01 00:00:00
abstract:OBJECTIVES:To examine the effect of reproductive history and use of hormonal therapies on the risk of hip and knee joint replacement for osteoarthritis. METHODS:A prospective study of 1.3 million women aged on average 56 years at recruitment and followed-up through linkage to routinely collected hospital admission rec...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2008.095653
更新日期:2009-07-01 00:00:00
abstract::Previous work has suggested that prior poor reproductive outcome may be a risk factor in rheumatoid arthritis (RA). A case-control study of 195 women with RA and 462 control women from two different sources is presented here. No increase in rates of spontaneous abortion was seen in the women with RA; indeed a protecti...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.49.1.12
更新日期:1990-01-01 00:00:00
abstract::The effect of immune complexes (IC) isolated from systemic lupus erythematosus (SLE) sera with polyethylene glycol and gel filtration on the chemotaxis and Fc receptor function of healthy monocytes was examined. Even at a low protein concentration (1 microgram/ml = 1 mg/l) ICs inhibit monocyte chemotaxis. ICs from pat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.5.729
更新日期:1984-10-01 00:00:00
abstract:OBJECTIVES:To investigate the effect of Janus kinase inhibitors (Jakinibs) on cardiovascular risk in adult patients with rheumatoid arthritis (RA) via a meta-analysis of randomised controlled trials (RCTs). METHODS:PubMed, Embase and Cochrane library were thoroughly searched for RCTs reporting safety issues in patient...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析
doi:10.1136/annrheumdis-2018-214846
更新日期:2019-08-01 00:00:00
abstract::Arthralgias have previously been reported in association with acne fulminans, but the following case in the first report of osseous lesions associated with this disease. The destructive bony lesion was rapid in onset but self-limited. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.39.4.403
更新日期:1980-08-01 00:00:00
abstract::Rheumatoid arthritis (RA) is diagnosed based on phenotypic characteristics. The 2010 ACR/EULAR criteria were derived with the aim of classifying RA earlier in the disease course than the 1987 ACR criteria. When reviewing thus far published validation studies, it is clear that the 2010 criteria can be fulfilled earlier...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-201426
更新日期:2012-10-01 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 develop evidence-based European League Against Rheumatism (EULAR) recommendations for the management of Behçet disease (BD) supplemented where necessary by expert opinion. METHODS:The multidisciplinary expert committee, a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), consisted ...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章,实务指引
doi:10.1136/ard.2007.080432
更新日期:2008-12-01 00:00:00
abstract::False positive results were obtained for HIV tests in two men with active systemic lupus erythematosus (SLE) who were suspected of being infected with HIV because of fever, weight loss, lymphadenopathy, and inflammatory myopathy. Enzyme linked immunosorbent assays (ELISAs) for HIV were twice positive when tested three...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.9.1071
更新日期:1992-09-01 00:00:00
abstract::T cells from patients with systemic lupus erythematosus exhibit a notable array of defects that probably contribute to the origin and development of the disease. Such abnormalities include an abnormal response to stimulation, aberrant expression of molecules that play key roles in intracellular signalling pathways, al...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2007.078493
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:In an unselected community sample of adults, to assess the role and importance of exposure to mechanical factors both at work and leisure in the aetiology of hip pain. METHOD:A population based prevalence case-control study. Cases and controls were identified from a population survey of 3847 subjects registe...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.62.4.322
更新日期:2003-04-01 00:00:00
abstract:OBJECTIVES:To evaluate changes in bone mineral density (BMD) in the hands, hip and spine after 1 and 2 years of follow-up, in relation to antirheumatic and antiresorptive therapies and disease and demographic variables in patients with recent-onset rheumatoid arthritis (RA). METHODS:Changes in BMD measured in metacarp...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2007.086348
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVES:To assess the reliability of the OMERACT ultrasound (US) definitions for the identification of calcium pyrophosphate deposition disease (CPPD) at the metacarpal-phalangeal, triangular fibrocartilage of the wrist (TFC), acromioclavicular (AC) and hip joints. METHODS:A web-based exercise and subsequent patien...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2017-212542
更新日期:2018-08-01 00:00:00
abstract:OBJECTIVE:To propose e-learning methods that address the fundamental problems related to sonographic training in rheumatology. METHODS:The project was designed for rheumatologists with strong motivation to learn ultrasound. A modular approach was constructed, consisting of a basic 3-day residential course, followed by...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.064568
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Rice bodies can occur in the joints in many rheumatic conditions, but they are most common in rheumatoid arthritis. They are generally believed to occur rarely in patients with osteoarthritis, but one study reported rice bodies with apatite crystals. OBJECTIVE:To report on a series of joint fluids with rice...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.5.387
更新日期:2002-05-01 00:00:00
abstract::This review assesses the risk assessment of cardiovascular disease (CVD) in rheumatoid arthritis (RA) and how non-invasive imaging modalities may improve risk stratification in future. RA is common and patients are at greater risk of CVD than the general population. Cardiovascular (CV) risk stratification is recommend...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2016-209744
更新日期:2017-07-01 00:00:00
abstract::In osteoarthritis (OA), adult articular chondrocytes undergo phenotypic modulation in response to alterations in the environment owing to mechanical injury and inflammation. These processes not only stimulate the production of enzymes that degrade the cartilage matrix but also inhibit repair. With the use of in vitro ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2008.098764
更新日期:2008-12-01 00:00:00
abstract:OBJECTIVE:To investigate the contribution of red blood cell (RBC) methotrexate polyglutamates (MTX PGs), RBC folate polyglutamates (folate PGs), and a pharmacogenetic index to the clinical status of patients with rheumatoid arthritis treated with MTX. METHODS:226 adult patients treated with weekly MTX for more than 3 ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2004.033399
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND:Progression of joint destruction in rheumatoid arthritis (RA) is partly heritable; knowledge of genetic factors may increase our understanding of the mechanisms underlying joint destruction. The activity of the Wnt/β-catenin pathway influences osteoblast differentiation. Dickkopf-1 (Dkk-1) and sclerostin (So...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析
doi:10.1136/annrheumdis-2012-202184
更新日期:2013-05-01 00:00:00
abstract:OBJECTIVES:Infectious agents like parvovirus have been implicated as exogenous factors that could trigger onset of systemic lupus erythematosus (SLE). A number of case reports describing a SLE-like presentation of acute human parvovirus B19 infection have been published, but no systematic investigation of the actual se...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.59.1.64
更新日期:2000-01-01 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:OBJECTIVE:To investigate the activation of NF-kappaB in the carrageenan rat air pouch model of inflammation in a time course experiment, and the effect of dexamethasone on NF-kappaB activation. METHODS:Air pouch tissue treated with carrageenan (inflamed tissue) was obtained from rats killed at days 1, 2, 3, 6, 14, 21,...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.59.4.303
更新日期:2000-04-01 00:00:00
abstract:OBJECTIVES:Leri's pleonosteosis (LP) is an autosomal dominant rheumatic condition characterised by flexion contractures of the interphalangeal joints, limited motion of multiple joints, and short broad metacarpals, metatarsals and phalanges. Scleroderma-like skin thickening can be seen in some individuals with LP. We u...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204309
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondylarthritides impose a great impact on the individual in addition to the costs on society, which may be reduced by effective pharmacological treatment. Industry-independent health economic studies should complement studies sponsored by indus...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.103473
更新日期:2010-02-01 00:00:00
abstract::A previous report that C3 activation products are demonstrable in the plasma of subjects with rheumatoid arthritis was reinvestigated using 2-dimensional immunoelectrophoresis. Initially it seemed that results were in agreement, but the occurrence of similar patterns in normal sera and poor reproducibility of results ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.1.18
更新日期:1978-02-01 00:00:00
abstract:OBJECTIVE:Antiphospholipid antibody (aPL) specificity for aPL-related events was evaluated in systemic lupus erythematosus (SLE). METHODS:A study was carried out on 105 patients affected with SLE comparing the prevalence of lupus anticoagulant (LA) and IgG and IgM anticardiolipin antibodies (aCL) between patients with...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.53.2.140
更新日期:1994-02-01 00:00:00
abstract::We describe a patient with rheumatoid arthritis and widespread joint and periarticular calcinosis related to self-medication with vitamin D, which was aggravated by oral phosphate therapy prescribed for her hypercalcaemia. Hydroxyapatite was shown in the synovial fluid from affected joints. The role played by tissue i...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.7.494
更新日期:1985-07-01 00:00:00
abstract::A nutritional assessment of 50 patients with rheumatoid arthritis (RA) showed evidence of malnutrition in 13 (26%), while all 50 control subjects had normal nutritional status. Of the anthropometric measurements the body-mass index and triceps skinfold thickness values in men and women were significantly reduced in RA...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.3.386
更新日期:1984-06-01 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