Abstract:
:Abnormalities in lymphocyte signaling cascades are thought to play an important role in the development of autoimmune disease. However, the large amount of cellular material needed for standard biochemical assessment of signaling status has made it difficult to evaluate putative abnormalities completely using primary lymphocytes. The development of technology to employ intracellular staining and flow cytometry to assess the signaling status of individual cells has now made it possible to delineate the perturbations that are present in lymphocytes from patients with autoimmune disease. As an example, human B cells from the Ramos B cell line and the periphery of systemic lupus erythematosus (SLE) patients or normal nonautoimmune controls were assessed for activation of the NF-kappaB and mitogen activated protein kinase (MAPK) signaling cascades by intracellular multiparameter flow cytometric analysis and biochemical Western blotting. In combination with fluorochrome conjugated antibodies specific for surface proteins that define B cell subsets, antibodies that recognize activated, or phosphorylated inhibitors of kappaB (IkappaB) as well as the extracellular regulated kinase (ERK), jun N-terminal kinase (JNK) or p38 MAPKs were used to stain fixed and permeabilized human B cells and analyze them flow cytometrically. Examination of the known signaling pathways following engagement of CD40 on human B cells confirmed that intracellular flow cytometry and Western blotting equivalently assay CD154-induced phosphorylation and degradation of IkappaB proteins as well as phosphorylation of the MAPKs ERK, JNK and p38. In addition, B cells from the periphery of SLE patients had a more activated status immediately ex vivo as assessed by intracellular flow cytometric analysis of phosphorylated ERK, JNK and p38 when compared with B cells from the periphery of normal, nonautoimmune individuals. Together, these results indicate that multiparameter intracellular flow cytometric analysis of signaling pathways, such as the NF-kappaB and MAPK cascades, can be used routinely to assess the activation status of a small number of cells and thus delineate abnormalities in signaling molecules expressed in primary lymphocytes from patients with autoimmune disease.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Grammer AC,Fischer R,Lee O,Zhang X,Lipsky PEdoi
10.1186/ar1155keywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
28-38issue
1eissn
1478-6354issn
1478-6362pii
ar1155journal_volume
6pub_type
杂志文章abstract:INTRODUCTION:Prostaglandin D synthase (PGDS) is responsible for the biosynthesis of PGD and J series, which have been shown to exhibit anti-inflammatory and anticatabolic effects. Two isoforms have been identified: hematopoietic- and lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study were to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2581
更新日期:2008-01-01 00:00:00
abstract::Prostaglandin E2 (PGE2) plays an important role in bone development and metabolism. To interfere therapeutically in the PGE2 pathway, however, knowledge about the involved enzymes (cyclooxygenases) and receptors (PGE2 receptors) is essential. We therefore examined the production of PGE2 in cultured growth plate chondr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1948
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Patient-reported outcomes measures, such as those provided by the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, have been found to be a reliable indicator of change during treatment, predictive of long-term outcomes, and the impact of psoriatic arthritis (PsA) on patients' lives. The objective...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02168-1
更新日期:2020-04-15 00:00:00
abstract:INTRODUCTION:The c-Jun N-terminal kinase (JNK) is a key regulator of matrix metalloproteinase (MMP) and cytokine production in rheumatoid arthritis (RA) and JNK deficiency markedly protects mice in animal models of arthritis. Cytokine-induced JNK activation is strictly dependent on the mitogen-activated protein kinase ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3750
更新日期:2012-02-21 00:00:00
abstract:INTRODUCTION:Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We thus decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3388
更新日期:2011-06-28 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:BACKGROUND:The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. MET...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02313-w
更新日期:2020-09-29 00:00:00
abstract:INTRODUCTION:C-reactive protein (CRP) is one of the biomarkers for the diagnosis and assessment of disease activity in rheumatoid arthritis (RA). CRP is not only the by-product of inflammatory response, but also plays proinflammatory and prothrombotic roles. The aim of this study was to determine the role of CRP on bon...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0563-z
更新日期:2015-03-04 00:00:00
abstract::Memory T cells display phenotypic heterogeneity. Surface antigens previously regarded as exclusive markers of naive T cells, such as L-selectin (CD62L), can also be detected on some memory T cells. Moreover, a fraction of CD45RO+ (positive for the short human isoform of CD45) memory T cells reverts to the CD45RA+ (pos...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar610
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3123
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expres...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1898-7
更新日期:2019-05-09 00:00:00
abstract::Joint space width (JSW) and narrowing (JSN) measurements on radiographs are currently the best way to assess disease severity or progression in hip osteoarthritis, yet we lack data regarding the most accurate and sensitive measurement technique. This study was conducted to determine the optimal radiograph and number o...
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/ar1831
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that is activated in the synovium in rheumatoid arthritis (RA) and promotes expression of various matrix metalloproteinases. In this study, we examined whether C/EBPβ mediates the expression of receptor activator of nuclear factor-kappa-B ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0532-6
更新日期:2015-02-17 00:00:00
abstract:INTRODUCTION:Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serve...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0414-3
更新日期:2014-08-20 00:00:00
abstract:INTRODUCTION:The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis. METHODS:Human CD14+ cells were isolated fro...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2936
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort. METHODS:In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 we...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/ar2773
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Cartilage damage impacts on patient disability in rheumatoid arthritis (RA). The aims of this magnetic resonance imaging (MRI) study were to investigate cartilage damage over three years and determine predictive factors. METHODS:A total of 38 RA patients and 22 controls were enrolled at t = 0 (2009). Afte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4462
更新日期:2014-01-30 00:00:00
abstract::Autoantibodies targeting intracellular proteins involved in key processes are detected in patients with idiopathic inflammatory myopathies. These myositis-specific autoantibodies have been increasingly demonstrated to correlate with distinct clinical phenotypes within the myositis spectrum. This review highlights the ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3275
更新日期:2011-03-18 00:00:00
abstract::T-helper (Th) lymphocytes contribute to arthritis pathogenesis by helping B cells to produce antibodies, by producing cytokines that activate effector cells involved in the destruction of cartilage and bone, and by contributing to osteoclast differentiation. There are murine models of arthritis, most notably collagen-...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3008
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:In recent decades, low-level laser therapy (LLLT) has been widely used to relieve pain caused by different musculoskeletal disorders. Though widely used, its reported therapeutic outcomes are varied and conflicting. Results similarly conflict regarding its usage in patients with nonspecific chronic low back ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s13075-015-0882-0
更新日期:2015-12-15 00:00:00
abstract::The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar2322
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Stem cell therapy is considered as a promising alternative to treat intervertebral disc degeneration (IDD). Extensive work had been done on identifying and comparing different types of candidate stem cells, both in vivo and in vitro. However, few studies have shed light on degenerative nucleus pulposus cells...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1677-x
更新日期:2018-08-16 00:00:00
abstract:INTRODUCTION:Broad-range rDNA PCR provides an alternative, cultivation-independent approach for identifying bacterial DNA in reactive and other form of arthritis. The aim of this study was to use broad-range rDNA PCR targeting the 16S rRNA gene in patients with reactive and other forms of arthritis and to screen for th...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2748
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:The goals of this study were to examine the oxemic regulation of Wnt signaling to explore whether Wnt signaling accelerates the age-related degeneration of nucleus pulposus cells, and if so, to define the mechanism underlying this effect. We investigated the expression of Klotho, a newly identified antiagi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3830
更新日期:2012-05-02 00:00:00
abstract::Treatment of Sjögren's syndrome is almost entirely symptomatic. A lack of true understanding of the underlying immunological pathology of the disease prevents directed therapy. Interleukin-21 (IL-21) is elevated in the serum of patients with this disease and is expressed by the lymphocytes infiltrating the salivary gl...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3518
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:UK guidelines recommend that all early active rheumatoid arthritis (RA) patients are offered combination disease-modifying antirheumatic drugs (DMARDs) and short-term corticosteroids. Anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA may differ in their treatment responses. We used d...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4439
更新日期:2014-01-16 00:00:00
abstract:INTRODUCTION:Interleukin-1 (IL-1) blockade is the treatment of choice of cryopyrin associated periodic syndromes (CAPS). Anti-IL-1 monoclonal antibody (canakinumab) was recently registered. However no clear data are available on the optimal schedule of administration of this drug. The aim of the present study was to an...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/ar4184
更新日期:2013-02-26 00:00:00
abstract:INTRODUCTION:Cartilage oligomeric matrix protein (COMP) is found at elevated concentrations in sera of patients with joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). We recently showed that COMP activates complement via the alternative pathway and that COMP-C3b complexes are present in sera of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3694
更新日期:2012-01-20 00:00:00
abstract:INTRODUCTION:Adjustment of infliximab dosage for individuals may be useful in improving therapeutic response in rheumatoid arthritis (RA). Herein, we aimed to determine whether measurement of infliximab serum concentration modifies the therapeutic decision and improves the control of disease activity. METHODS:RA patie...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar2867
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02354-1
更新日期:2020-12-09 00:00:00