Abstract:
BACKGROUND:Signs of inflammation in cerebrospinal fluid (CSF) of rheumatoid arthritis patients correlate positively with fatigue, a central nervous system (CNS)-related symptom that can be partially suppressed by TNF blockade. This suggests a possible role for CNS inflammation in arthritis that may be affected by TNF blockade. We therefore investigated the effects of TNF blockade on the arthritis CSF proteome and how candidate proteins related to clinical measures of disease activity and inflammation. METHODS:Mass spectrometry-based quantitative proteomic analysis was performed on CSF from seven polyarthritis patients before and during infliximab treatment. Treatment-associated proteins were identified using univariate (Wilcoxon signed rank test) and multivariate (partial least squares discriminant analysis (PLS-DA)) strategies. Relations between selected candidate proteins and clinical measures were investigated using the Spearman correlations. Additionally, selected proteins were cross-referenced to other studies investigating human CSF in a thorough literature search to ensure feasibility of our results. RESULTS:Univariate analysis of arthritis CSF proteome revealed a decrease of 35 proteins, predominantly involved in inflammatory processes, following TNF blockade. Seven candidate proteins, Contactin-1 (CNTN1), fibrinogen gamma chain (FGG), hemopexin (HPX), cell adhesion molecule-3 (CADM3), alpha-1B-glycoprotein (A1BG), complement factor B (CFB), and beta-2-microglobulin (B2M), were selected for further studies based on identification by both univariate and multivariate analyses and reported detection in human CSF and known associations to arthritis. Decreased levels of FGG and CFB in CSF after treatment showed strong correlations with both erythrocyte sedimentation rate and disability scores, while CNTN1 and CADM3 were associated with pain. CONCLUSION:Several immune-related proteins in the CSF of arthritis patients decreased during TNF blockade, including FGG and CFB that both correlated strongly with systemic inflammation. Our findings stress that also intrathecal inflammatory pathways are related to arthritis symptoms and may be affected by TNF blockade.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Estelius J,Lengqvist J,Ossipova E,Idborg H,Le Maître E,Andersson MLA,Brundin L,Khademi M,Svenungsson E,Jakobsson PJ,Lampa Jdoi
10.1186/s13075-019-1846-6subject
Has Abstractpub_date
2019-02-15 00:00:00pages
60issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-019-1846-6journal_volume
21pub_type
杂志文章abstract:INTRODUCTION:NLRP3 plays a role in sensing various pathogen components or stresses in the innate immune system. Once activated, NLRP3 associates with apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and procaspase-1 to form a large protein complex termed inflammasome. Although some ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4483
更新日期:2014-02-12 00:00:00
abstract::The changes occurring in the field of rheumatoid arthritis (RA) over the past decade or two have encompassed new therapies and, in particular, a new look at the clinical characteristics of the disease in the context of therapeutic improvements. It has been shown that composite disease activity indices have special mer...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2535
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:TNFα is a proinflammatory cytokine that plays a central role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of certolizumab pegol, a TNFα blocker, on endothelial cell function and angiogenesis. METHODS:Human dermal microvascular endothelial cells (HMVECs) were stimulated wit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3812
更新日期:2012-04-25 00:00:00
abstract::Established rheumatoid arthritis (RA) is associated with a doubled cardiovascular risk. However, data about the cardiovascular risk in early RA are scarce. Preclinical atherosclerosis can be reliably assessed with the carotid intima media thickness (cIMT), and the cIMT is a well-validated predictor of cardiovascular e...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3126
更新日期:2010-01-01 00:00:00
abstract::Systemic lupus erythematosus is a prototypic autoimmune disease characterized by autoantibody production and immune complex formation/deposition in target organs such as the kidney. Resultant local inflammation then leads to organ damage. Nephritis, a major cause of morbidity and mortality in patients with lupus, occu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3528
更新日期:2011-01-01 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:During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful. Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common. Endocannabinoids have the...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0437-9
更新日期:2014-09-27 00:00:00
abstract:INTRODUCTION:In the present systematic review and meta-analysis, we assessed the effectiveness of different forms of balneotherapy (BT) and hydrotherapy (HT) in the management of fibromyalgia syndrome (FMS). METHODS:A systematic literature search was conducted through April 2013 (Medline via Pubmed, Cochrane Central R...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/ar4603
更新日期:2014-07-07 00:00:00
abstract:INTRODUCTION:miR-146a is one of the first identified miRNAs expressed differentially in osteoarthritis (OA) cartilage. However, the role it plays in OA pathogenesis is not clear. The aim of this study is to identify a molecular target of miR-146a, thereby elucidating its function in chondrocytes during OA pathogenesis....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3798
更新日期:2012-04-16 00:00:00
abstract:INTRODUCTION:The immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4067
更新日期:2012-10-19 00:00:00
abstract::Articular calcification correlates with osteoarthritis (OA) severity but its exact role in the disease process is unclear. In examining OA meniscal cell function, Sun and colleagues have shown recently that meniscal cells from end-stage OA subjects can generate calcium crystals and that genes involved in calcification...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2993
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Glomerulonephritis is one of the major complications and causes of death in systemic lupus erythematosus (SLE) and is characterized by glomerulosclerosis, interstitial fibrosis, and tubular atrophy, along with severe persistent proteinuria. DZ2002 is a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) in...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1820-3
更新日期:2019-01-29 00:00:00
abstract::Magnetic resonance imaging bone marrow edema is an imaging feature that has been described in many conditions, including osteomyelitis, overuse syndromes, avascular necrosis, trauma, and inflammatory arthritides. In rheumatoid arthritis (RA), bone edema has special significance as it has been shown to be a common and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4035
更新日期:2012-09-28 00:00:00
abstract:BACKGROUND:The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of systemic lupus erythematosus (SLE) patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (Crithidia Luciliae immunofluorescence test (CLIFT)). To overcom...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1117-8
更新日期:2016-10-04 00:00:00
abstract:BACKGROUND:Determining the association between body composition and low back pain (LBP) will improve our understanding of the mechanisms by which obesity affects LBP, and inform novel approaches to managing LBP. The aim of this study was to examine the relationship between body composition and LBP intensity and disabi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1242-z
更新日期:2017-02-10 00:00:00
abstract::An impaired differentiation of naive CD4+ T cells towards Th2 cells may contribute to the chronic tissue-destructive T-cell activity in rheumatoid arthritis (RA). The differentiation of naive CD4+ T cells into memory Th2 cells by IL-7 in comparison with that by IL-4 was studied in RA patients and in healthy controls. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar790
更新日期:2003-01-01 00:00:00
abstract::As translational clinical researchers familiar with the risk-benefit of hematopoietic stem cell transplantation in autoimmune diseases, we are intrigued by the recent report of umbilical cord mesenchymal stem cell (UC-MSC) transplantation in treatment-refractory systemic lupus erythematosus nephritis by Wang and colle...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar4677
更新日期:2014-07-30 00:00:00
abstract:BACKGROUND:During pregnancy, many patients with rheumatoid arthritis (RA) experience disease improvement, whereas patients with ankylosing spondylitis often suffer from persistent active disease. Here we investigated whether pregnancy-related changes in disease activity were associated with changes in the proportion an...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0925-1
更新日期:2016-01-22 00:00:00
abstract:INTRODUCTION:Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed withi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0575-8
更新日期:2015-03-23 00:00:00
abstract:BACKGROUND:The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZB x NZW) F1 murine lupus model. METHODS:Female NZB/W F1 mice (11 weeks old) were treated daily with 25 or 50 mg/kg oral spironolactone or vehicle. Proteinuria...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2353
更新日期:2008-01-01 00:00:00
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 ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1155
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Pain remains the most important problem for people with rheumatoid arthritis (RA). Active inflammatory disease contributes to pain, but pain due to non-inflammatory mechanisms can confound the assessment of disease activity. We hypothesize that augmented pain processing, fibromyalgic features, poorer menta...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0525-5
更新日期:2015-01-20 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: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:OBJECTIVE:To assess the associations between aspartate transaminase/alanine transaminase ratio (DRR) and mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). PATIENTS AND METHODS:This was a retrospective cohort study, which included 522 patients with PM/DM-ILD whose...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02286-w
更新日期:2020-09-20 00:00:00
abstract:INTRODUCTION:Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4368
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:The efficacy and the optimal type and volume of aerobic exercise (AE) in fibromyalgia syndrome (FMS) are not established. We therefore assessed the efficacy of different types and volumes of AE in FMS. METHODS:The Cochrane Library, EMBASE, MEDLINE, PsychInfo and SPORTDISCUS (through April 2009) and the re...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/ar3002
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Autophagy induction is an effective approach for OA therapy. IL-1β is one of the major inflammatory cytokines linked to OA pathological progression, and its receptor blockade interrupts OA cartilage destruction. The objective of this study was to decipher the link between autophagy and regulatory mechanism o...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1952-5
更新日期:2019-07-10 00:00:00
abstract:INTRODUCTION:Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial cit...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar3702
更新日期:2012-01-27 00:00:00
abstract::In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1772
更新日期:2005-01-01 00:00:00