Abstract:
OBJECTIVE:An increased proportion of circulating follicular helper T (Tfh) cells was reported in rheumatoid arthritis (RA), but it remains uncertain how Tfh cells affect antibody hyposialylation. We investigated the regulation of autoantibody hyposialylation by Tfh cells in RA using murine model. METHODS:Behaviours of Tfh cells and their function on B cell promotion were analysed. Change of arthritogenicity and sialylation of autoantibodies during the course of arthritis was examined by mass spectrometry. Tfh-mediated regulation of hyposialylation was investigated, and the responsible cell surface molecule was specified both in vitro and in vivo. The relation between circulating Tfh cells and hyposialylation was analysed in patients with RA. RESULTS:An increase in Tfh, particularly interleukin-17 producing Tfh (Tfh17) cells, at the onset of arthritis and their enhancement of autoantibody production were found. Autoantibodies at the onset phase demonstrated stronger inflammatory properties than those at the resolution phase, and mass spectrometric analysis revealed their difference in sialylation. In vitro coculture showed enhanced hyposialylation by the Tfh cells via OX40, which was highly expressed in the Tfh and Tfh17 cells. Blockade of OX40 prevented the development of arthritis with reduction in Tfh17 cells and recovery of autoantibody sialylation. Analysis of patients with RA showed abundance of OX40-overexpressing Tfh17 cells, and their proportion correlated negatively with the expression of α2,6-sialyltransferase 1, an enzyme responsible for sialylation. CONCLUSIONS:OX40 expressed on Tfh cells can regulate autoantibody sialylation and play a crucial role in the development of autoimmune arthritis.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Kurata I,Matsumoto I,Ohyama A,Osada A,Ebe H,Kawaguchi H,Kaneko S,Kondo Y,Tsuboi H,Tomioka A,Kaji H,Sumida Tdoi
10.1136/annrheumdis-2019-215195subject
Has Abstractpub_date
2019-11-01 00:00:00pages
1488-1496issue
11eissn
0003-4967issn
1468-2060pii
annrheumdis-2019-215195journal_volume
78pub_type
杂志文章abstract:BACKGROUND:Certain sequences present in the hypervariable region of human leucocyte antigen (HLA)-DRB1 known as the shared epitope (SE) are hypothesised to increase the risk of rheumatoid arthritis (RA), whereas alleles encoding aspartic acid at position 70 (D70 alleles) may have a protective effect. METHODS:Patient H...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.067603
更新日期:2007-11-01 00:00:00
abstract::Twenty-five patients (22 males and 3 females) are described who had 'unclassifiable' seronegative peripheral arthritis affecting mainly the large joints of the lower limbs with other typical features of spondyloarthropathies such as heel pain, low back pain, and mucosal ulcers. But their disorders could not be diagnos...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.42.6.640
更新日期:1983-12-01 00:00:00
abstract:OBJECTIVE:To determine the relationship of disease activity to infections in patients with rheumatoid arthritis (RA). METHODS:From the CORRONA database, the incidence of physician-reported infections in RA patients on stable disease-modifying antirheumatic drug, biological, and corticosteroid therapy for at least 6 mo...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2010.128637
更新日期:2011-05-01 00:00:00
abstract:OBJECTIVES:To compare the prevalence of osteoarthritis (OA) of the hip, tibiofemoral and patellofemoral joints in a skeletal population. METHODS:A total of 785 adult English skeletons (695 Saxon or Mediaeval origin) were examined for OA using established criteria. RESULTS:Twenty nine skeletons had hip OA, compared wi...
journal_title:Annals of the rheumatic diseases
pub_type: 历史文章,杂志文章
doi:10.1136/ard.53.9.612
更新日期:1994-09-01 00:00:00
abstract:OBJECTIVES:Smoking increases the risk of developing rheumatoid arthritis (RA) and worsens the course of the disease. In the current study we analysed whether smoking can affect gene expression directly in the joints. METHODS:Synovial fibroblasts were incubated with 5% cigarette smoke extract and changes in gene expres...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204486
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVES:To study the gene-environment interaction of tobacco exposure and shared epitope on autoantibodies in patients with rheumatoid arthritis and undifferentiated arthritis. METHODS:From incident cases of arthritis (n = 1305), patients who did not fulfil any classification criteria (undifferentiated arthritis (n...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.041079
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVE:To investigate the predictive value of discordance between (1) tender and swollen joint count and (2) patient's and evaluator's global assessment on remission in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS:From the prospective, multicentre Norwegian-Disease-Modifying Antirh...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2016-210283
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVE:Transient receptor potential canonical 5 (TRPC5) is functionally expressed on a range of cells including fibroblast-like synoviocytes, which play an important role in arthritis. A role for TRPC5 in inflammation has not been previously shown in vivo. We investigated the contribution of TRPC5 in arthritis. MET...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-208886
更新日期:2017-01-01 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:OBJECTIVES:To estimate the prevalence and incidence of systemic sclerosis (SSc) in southern Sweden. METHODS:In Skåne, the southernmost region of Sweden (total population 1.2 million), healthcare provided is registered in the Skåne Healthcare Register. We identified all Skåne residents who had received an International...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-203618
更新日期:2014-10-01 00:00:00
abstract:OBJECTIVES:To evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics. METHODS:This randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6-8 mg...
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-2012-202433
更新日期:2014-03-01 00:00:00
abstract:OBJECTIVE:To analyse matrix metalloproteinases (MMPs) and tissue inhibitor-1 of MMPs (TIMP-1) levels in the systemic circulation and synovial fluid (SF) of patients with RA and to compare these levels with inflammatory and collagen degradation markers. METHODS:ProMMP-1, -2, -3, -8, -9, TIMP-1, levels of MMP/alpha(2)-m...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.013243
更新日期:2004-07-01 00:00:00
abstract:OBJECTIVE:To assess the effects of tumour necrosis factor (TNF) antagonist therapy on B lymphocyte stimulator (BLyS) expression in patients with rheumatoid arthritis (RA). METHODS:Blood from 38 patients with RA from a single centre was collected prior to and following initiation of TNF antagonist therapy. Plasma BLyS ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.079954
更新日期:2008-08-01 00:00:00
abstract:OBJECTIVE:To determine if a new inhibitor, esculetin (EST), can block resorption of cartilage. METHODS:Interleukin 1alpha (IL1alpha, 0.04-5 ng/ml) and oncostatin M (OSM, 0.4-50 ng/ml) were used to stimulate the release of proteoglycan and collagen from bovine nasal cartilage and human articular cartilage in explant cu...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.2.158
更新日期:2001-02-01 00:00:00
abstract:OBJECTIVE:B lymphocytes have been implicated in the pathogenesis of lupus and other autoimmune diseases, resulting in the introduction of B cell-directed therapies. Epratuzumab, a humanised anti-CD22 monoclonal antibody, is currently in clinical trials, although its effects on patients' B cells are not completely under...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.2007.075762
更新日期:2008-04-01 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::Polymorphonuclear leucocytes (PMNs), which predominate in inflammatory synovial fluid, can degrade cartilage. This was measured by a novel in vitro model; PMNs were incubated for up to one hour with 2 or 3 microns sections of cartilage and the glycosaminoglycan loss determined by microdensitometry after alcian blue st...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.52.1.27
更新日期:1993-01-01 00:00:00
abstract::Information has been collected on 10 patients, 9 with marrow depression and 1 in whom the diagnosis was presumed. Six of the 10 patients died. The sequentially recorded blood counts on at least 5 of the patients showed a downward trend of the white cell and platelet counts while D-penicillamine was still being adminis...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.38.3.232
更新日期:1979-06-01 00:00:00
abstract::Platelet serotonin concentrations were measured in 43 patients with systemic sclerosis, in 11 patients with primary Raynaud's phenomenon, and in 38 normal controls. Patients with the CREST variant (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) had significantly lower platele...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.48.7.586
更新日期:1989-07-01 00:00:00
abstract:OBJECTIVES:Assess golimumab's long-term efficacy/safety in psoriatic arthritis (PsA). METHODS:Adults with active PsA (≥3 swollen and tender joints, active psoriasis) were randomly assigned to subcutaneous placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks (q4wks) through wk20. All patients received golimumab ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2013-204902
更新日期:2014-09-01 00:00:00
abstract:OBJECTIVE:To investigate the role of CD8 cell subsets in the pathogenesis of rheumatoid arthritis (RA) and the phenotypes of T cells adherent or non-adherent to the target cells (endothelial cells and synovial cells) pre-treated with IL-1 beta. METHODS:The expression of S6F1 on CD8 cells and that of an activation mark...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.53.12.816
更新日期:1994-12-01 00:00:00
abstract:OBJECTIVES:To evaluate the risk of septic arthritis (SA) in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. METHODS:Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, the authors compared the risk of SA between 11 ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2011.152769
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that high concentrations of extracellular inorganic pyrophosphate (PPi), which associate with increased cell synthesis and turnover in cartilage, may act as a marker for structural outcome in knee osteoarthritis (OA). METHOD:One hundred and thirty five consecutive patients referred to ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.55.7.432
更新日期:1996-07-01 00:00:00
abstract::Today, patients' functioning is a central issue in medicine. Concepts, classifications, and measurements of functioning and health, such as the International Classification of Functioning, Disability and Health (ICF) are of prime importance in clinical practice, teaching, and research. This report compares the content...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2004.028233
更新日期:2004-11-01 00:00:00
abstract::The question 'Does the use of second-line therapy confer long-term benefit on outcome measures in rheumatoid arthritis?' remains unanswered. The major obstacle which prevents collection of the necessary data is the lack of a suitable control group. In this report experience with three 'second-line placebo groups' is d...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,评审
doi:10.1136/ard.44.2.134
更新日期:1985-02-01 00:00:00
abstract:BACKGROUND:In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2014-205681
更新日期:2015-12-01 00:00:00
abstract:OBJECTIVES:This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA). METHODS:Treatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or acti...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2020-218510
更新日期:2020-10-28 00:00:00
abstract:INTRODUCTION:The anticyclic citrullinated peptide 2 (anti-CCP2) assay is a generic test for antibodies to citrullinated proteins, among which there is a subset of about 50% with antibodies to citrullinated enolase peptide 1 (CEP-1). The anti-CEP-1 positive subset is strongly associated with the HLA-DRB1 shared epitope ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2010.138909
更新日期:2011-06-01 00:00:00
abstract::Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocortic...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章,评审
doi:10.1136/ard.2009.126532
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients. METHODS:A systematic literature review was performed using predefined inclusion criteria to identify randomised...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2010.146043
更新日期:2011-09-01 00:00:00