Abstract:
INTRODUCTION:Rituximab (RTX) therapy of rheumatoid arthritis (RA) exhibits enhanced effectiveness in seropositive patients. Using patient sera, we tested if this improved efficacy was associated with enhanced RTX mediated complement-dependent cytotoxicity (RTX-CDC). METHODS:We developed an in vitro assay for RTX-CDC using patient sera and the Daudi human B cell line. Using propidium iodide uptake and flow cytometry, we compared RTX-CDC with rheumatoid factor (RF)+ sera relative to normal volunteer, non-RA and RF- sera. Additional studies examined mixing studies of RF+ and RF- sera, as well as the effect of monoclonal IgA or IgM RF. Finally, the effect of RF on RTX mediated trogocytosis of normal B cells was evaluated. RESULTS:Using human sera, addition of RTX resulted in rapid and profound (>50%) Daudi cell death that was complement dependent. Surprisingly, RF+ patient sera exhibited reduced RTX-CDC relative to RF- sera, with an inverse relationship of RTX-CDC and RF titer. Mixing studies indicated the presence of an inhibitor of RTX-CDC in RF+ sera. The addition of monoclonal IgM or IgA RF to RF- sera markedly inhibited RTX-CDC. This effect was specific for RF binding to the Fc portion of RTX as it was not apparent with the F(ab)' domains of RTX engineered onto IgG3 heavy chain. RF also modestly inhibited RTX mediated trogocytosis. CONCLUSIONS:Contrary to expectations, RF+ sera exhibits reduced RTX-CDC due to the presence of RF. The enhanced efficacy of RTX in seropositive RA patients cannot be attributed to improved B cell depletion through CDC. This result indicates that high RF levels may potentially modulate the efficacy of any therapeutic monoclonal antibody dependent on Fc effector function.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Jones JD,Shyu I,Newkirk MM,Rigby WFdoi
10.1186/ar4152subject
Has Abstractpub_date
2013-01-25 00:00:00pages
R20issue
1eissn
1478-6354issn
1478-6362pii
ar4152journal_volume
15pub_type
杂志文章abstract:INTRODUCTION:The endoplasmic reticulum (ER) stress-response, evoked in mice by the overexpression of class I major histocompatibility complex antigen (MHC-I), was proposed as a major mechanism responsible for skeletal muscle damage and dysfunction in autoimmune myositis. The present study was undertaken to characterize...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2963
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:High levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA). Survivin is a sensitive predictor of joint damage and persistent disease activity. Survivin-positive patients are often poor responders to antirheumatic and biological treatment. The ai...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4438
更新日期:2014-01-16 00:00:00
abstract:INTRODUCTION:Physical activity has been recommended to patients with knee osteoarthritis for improving their symptoms. However, it is still controversial if physical activity has effects on joint structures including cartilage volume. The aim of this study was to describe the associations between physical activity and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0813-0
更新日期:2015-10-26 00:00:00
abstract:INTRODUCTION:Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a p...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/ar2740
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02351-4
更新日期:2020-10-19 00:00:00
abstract::Synovial fluid from patients with various arthritides contains procoagulant, cell-derived microparticles. Here we studied whether synovial microparticles modulate the release of chemokines and cytokines by fibroblast-like synoviocytes (FLS). Microparticles, isolated from the synovial fluid of rheumatoid arthritis (RA)...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1706
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Disease-modifying antirheumatic drugs (DMARDs) have become the treatment standard for patients with rheumatoid arthritis (RA). Although several general-population studies document that a large population of patients diagnosed with RA do not use DMARDs, little is known about this group. We explored the char...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4459
更新日期:2014-01-29 00:00:00
abstract:BACKGROUND:Elevated B lymphocyte stimulator (BLyS) levels in patients with systemic lupus erythematosus (SLE) correlate positively with disease activity; BLyS expression is directly linked to interferon (IFN) pathway activation. This post hoc meta-analysis of BLISS-52 and BLISS-76 explored the relationship between base...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02177-0
更新日期:2020-05-04 00:00:00
abstract:INTRODUCTION:Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruct...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4474
更新日期:2014-02-05 00:00:00
abstract:INTRODUCTION:Despite the substantial prevalence of gout in the ageing female population, female hormonal influence has not been comprehensively examined. We evaluated and quantified the potential independent association between menopause, postmenopausal hormone use and serum uric acid levels in a nationally representat...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2519
更新日期:2008-01-01 00:00:00
abstract::The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1 production and MMP-13 production was investigated in human osteoarthritis chondrocytes. The cells were isolated from human articular cartilage obtained at surgery and were cultured in the absence or presence of ET-1 with or without inhibi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1489
更新日期:2005-01-01 00:00:00
abstract::Collagen-induced arthritis (CIA), an approved animal model for rheumatoid arthritis, is thought to be a T cell-dependent disease. There is evidence that CD8+ T cells are a major subset controlling the pathogenesis of CIA. They probably contribute to certain features of disease, namely tissue destruction and synovial h...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1758
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Interstitial lung disease in systemic sclerosis (SSc-ILD) is a major cause of SSc-related death. Imunosuppressive treatment (IS) is used in patients with SSc for various organ manifestations mainly to ameliorate progression of SSc-ILD. Data on everyday IS prescription patterns and clinical courses of lung fu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1517-z
更新日期:2018-01-30 00:00:00
abstract:INTRODUCTION:Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accurac...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4383
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Synovial fibroblasts play a key role in joint destruction and regulation of the inflammatory infiltrate in established rheumatoid arthritis (RA). The mechanisms by which this occurs in the earliest stages of RA are largely unknown. We investigated the role of Dickkopf-related protein 1 (DKK1) produced by syn...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0915-3
更新日期:2016-01-19 00:00:00
abstract:INTRODUCTION:The aim of this study was to investigate the role of hand bone mineral density (BMD) loss analyzed with digital X-ray radiogrammetry (DXR) in early rheumatoid arthritis (RA) as a predictor for progression of joint damage. METHODS:In 379 patients with early RA, baseline and one-year hand BMD was measured w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/ar4058
更新日期:2012-10-15 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) patients have lower bone mineral density and increased fracture risk when compared with healthy individuals, due to distinct factors and mechanisms. Bone remodeling is a tightly orchestrated process dependent on several factors, including the balance between receptor acti...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/ar3500
更新日期:2011-01-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production and inflammatory cell infiltration in target organs, such as the kidneys and brain. T cells are critical players in SLE pathophysiology as they regulate...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3251
更新日期:2011-03-17 00:00:00
abstract:BACKGROUND:We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4+ T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1278-0
更新日期:2017-04-11 00:00:00
abstract::Pegloticase is a powerful but underutilized weapon in the rheumatologist's armamentarium. The drug's immunogenicity leads to neutralizing antibody formation and rapid loss of efficacy in roughly one-half of all patients, which remains an impediment to broader use. New data, however, suggest that drug survival might im...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar4572
更新日期:2014-05-30 00:00:00
abstract:INTRODUCTION:The present study aimed to explore a possible role for IL-21 producing Th-cells in the immunopathogenesis of granulomatosis with polyangiitis (GPA). METHODS:Peripheral blood from 42 GPA patients in remission and 29 age-matched healthy controls (HCs) were stimulated in vitro, and the frequencies of IL-21 p...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4247
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:Autoantibodies against mutated and citrullinated vimentin (MCV) represent a novel diagnostic marker for rheumatoid arthritis (RA). Recently, an increased sensitivity for anti-MCV compared to autoantibodies against cyclic citrullinated peptides (anti-CCP2) was shown in cohorts of patients with early RA and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3057
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Objectives were to investigate whether interactions between human osteoarthritic chondrocytes and 4-hydroxynonenal (HNE)-modified type II collagen (Col II) affect cell phenotype and functions and to determine the protective role of carnosine (CAR) treatment in preventing these effects. METHODS:Human Col I...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3173
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:In cross-sectional studies, patients with rheumatoid arthritis (RA) have higher coronary artery calcium (CAC) than controls. However, their rate of progression of CAC and the predictors of CAC progression have heretofore remained unknown. METHODS:Incidence and progression of CAC were compared in 155 patie...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4314
更新日期:2013-09-25 00:00:00
abstract:INTRODUCTION:Serious infection, cardiovascular disease, and mortality are increased in rheumatoid arthritis (RA). Whether RA affects the risk for these complications after total joint arthroplasty (TJA) is unknown, we hypothesize that it does. We compared the occurrence of 30-day postoperative complications and mortali...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4385
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and organs. Increase in oxidative stress and platelet-derived growth factor receptor (PDGFR) activation promote collagen I (Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active metabolite...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0411-6
更新日期:2014-01-01 00:00:00
abstract:INTRODUCTION:Mesenchymal stem cells (MSCs) can differentiate into various connective tissue cells. Several techniques have been used for the clinical application of MSCs in articular cartilage repair; however, there are many issues associated with the selection of the scaffold material, including its ability to support...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3735
更新日期:2012-02-07 00:00:00
abstract::Human T cell leukaemia virus type I (HTLV-I) is known to be involved in late-onset chronic polyarthritis as HTLV-I-associated arthropathy. However, it is unclear whether HTLV-I infection could modify the pathophysiology of osteoarthritis (OA). In this study we compared several inflammatory cytokines, such as C-termina...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1193
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term stru...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2043-3
更新日期:2019-12-04 00:00:00
abstract:INTRODUCTION:Recent advances suggest that the cellular redox state may play a significant role in the progression of fibrosis in systemic sclerosis (SSc). Another, and as yet poorly accounted for, feature of SSc is its overlap with thyroid abnormalities. Previous reports demonstrate that hypothyroidism reduces oxidant ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4300
更新日期:2013-09-16 00:00:00