Abstract:
INTRODUCTION:Properdin amplifies the alternative pathway of complement activation. In the present study, we evaluated its role in the development of collagen antibody-induced arthritis (CAIA). METHODS:Arthritis was induced by intraperitoneal injection of a collagen antibody cocktail into properdin-deficient (KO) and wild-type (WT) C57BL/6 mice. Symptoms of disease were evaluated daily. The degree of joint damage was assessed histologically and with immunostaining for bone-resorption markers. Phenotypes of cell populations, their receptor expression, and intracellular cytokine production were determined with flow cytometry. Osteoclast differentiation of bone marrow (BM) precursors was evaluated by staining for tartrate-resistant acid phosphatase (TRAP). RESULTS:Properdin-deficient mice developed less severe CAIA than did WT mice. They showed significantly improved clinical scores and downregulated expression of bone-resorption markers in the joints at day 10 of disease. The frequencies of Ly6G⁺CD11b⁺ cells were fewer in BM, blood, and synovial fluid (SF) of KO than of WT CAIA mice. The receptor activator of nuclear factor κB ligand (RANKL) was downregulated on arthritic KO neutrophils from BM and the periphery. Decreased C5a amounts in KO SF contributed to lower frequencies of CD5aR⁺-bearing neutrophils. In blood, surface C5aR was detected on KO Ly6G⁺ cells as a result of low receptor engagement. Circulating CD4⁺ T cells had an altered ability to produce interleukin (IL)-17 and interferon (IFN)-γ and to express RANKL. In KO CAIA mice, decreased frequencies of CD4⁺ T cells in the spleen were related to low CD86 expression on Ly6GhighCD11b⁺ cells. Arthritic KO T cells spontaneously secreted IFN-γ but not IL-17 and IL-6, and responded to restimulation with less-vigorous cytokine production in comparison to WT cells. Fewer TRAP-positive mature osteoclasts were found in KO BM cell cultures. CONCLUSIONS:Our data show that the active involvement of properdin in arthritis is related to an increased proinflammatory cytokine production and RANKL expression on immune cells and to a stimulation of the RANKL-dependent osteoclast differentiation.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Dimitrova P,Ivanovska N,Belenska L,Milanova V,Schwaeble W,Stover Cdoi
10.1186/ar3926subject
Has Abstractpub_date
2012-07-25 00:00:00pages
R173issue
4eissn
1478-6354issn
1478-6362pii
ar3926journal_volume
14pub_type
杂志文章abstract:BACKGROUND:Ultrasound (US) is a sensitive method for detecting joint/tendon inflammation in patients with rheumatoid arthritis (RA). Subclinical inflammation is often found in patients with RA in composite score remission. The purpose of the present study was to explore whether US of only the hands is sufficient to ide...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1428-4
更新日期:2017-10-04 00:00:00
abstract:INTRODUCTION:The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a plays a central role. In this study, plasma and urinary levels of C5a as well as renal C5a receptors (CD88 and C5L2) expression were investigated in patients wi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3873
更新日期:2012-06-12 00:00:00
abstract::I comment on the well-designed trial by Alda and colleagues reported in a recent issue of Arthritis Research and Therapy which demonstrated some benefits of cognitive-behavioral therapy (CBT) for fibromyalgia (FM). CBT in this and other studies provides statistically significant but rather modest benefits for FM. This...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3511
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Factors associated with care concordant with the American College of Rheumatology (ACR) recommendations for the use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) are unknown. METHODS:We identified a national cohort of biologic-naive patients with RA with visits between Decem...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0992-3
更新日期:2016-04-26 00:00:00
abstract::Hypoxia, which leads to dysfunctional cell metabolism, and complement activation both play central roles in the pathogenesis of rheumatoid arthritis (RA). Recent studies have reported that mice deficient for the complement-inhibitory protein CD59 show enhanced susceptibility to antigen-induced arthritis and reported t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2019
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Risk prediction algorithms increase understanding of which patients are at greatest risk of a harmful outcome. Our goal was to create a clinically useful prediction algorithm for structural progression of knee osteoarthritis (OA), using medial joint space loss as a proxy; and to quantify the benefit of inclu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-017-1291-3
更新日期:2017-05-16 00:00:00
abstract:INTRODUCTION:Tumor necrosis factor (TNF) and, possibly, lymphotoxin alpha (LTα) signaling contribute to inflammation and rheumatoid arthritis (RA) pathogenesis. Pateclizumab (anti-lymphotoxin- alpha; MLTA3698A) is a humanized monoclonal antibody that blocks and depletes anti-LTα. This phase 2, randomized, head-to-head,...
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/s13075-014-0467-3
更新日期:2014-10-30 00:00:00
abstract:INTRODUCTION:In this study, we aimed to determine the relationship between flow-mediated endothelium-dependent vasodilatation (FMD) and carotid artery intima-media wall thickness (IMT), two surrogate markers of atherosclerosis, in a series of Spanish patients with rheumatoid arthritis (RA) without clinically evident ca...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3382
更新日期:2011-06-22 00:00:00
abstract:INTRODUCTION:We and others have previously shown that antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and in a more recent study we reported that individuals who subsequently developed RA had increased concentrations of several cytokines and chemokines ye...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3237
更新日期:2011-02-03 00:00:00
abstract:INTRODUCTION:The major histocompatibility complex (H-2d) and non-major histocompatibility complex genetic backgrounds make the BALB/c strain highly susceptible to inflammatory arthritis and spondylitis. Although different BALB/c colonies develop proteoglycan-induced arthritis and proteoglycan-induced spondylitis in res...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2613
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultra...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3742
更新日期:2012-02-15 00:00:00
abstract::Genomewide association studies (GWAS) have proven a powerful hypothesis-free method to identify common disease-associated variants. Even quite large GWAS, however, have only at best identified moderate proportions of the genetic variants contributing to disease heritability. To provide cost-effective genotyping of com...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3204
更新日期:2011-02-01 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
abstract::This prospective study examined the association between physical activity and the incidence of self-reported stiff or painful joints (SPJ) among mid-age women and older women over a 3-year period. Data were collected from cohorts of mid-age (48-55 years at Time 1; n = 4,780) and older women (72-79 years at Time 1; n =...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2154
更新日期:2007-01-01 00:00:00
abstract::The objective of this study was to evaluate the safety and possible efficacy of IFN-beta-1a for the treatment of patients with rheumatoid arthritis (RA). Twenty-two patients with active RA were enrolled in a phase II randomized, double-blind, placebo-controlled trial of 30 microg IFN-beta-1a by weekly self-injection f...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1026
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Rheumatic diseases are among the most common and debilitating health problems in the United States. These diseases are chronic, can result in severe decrements of physical and psychosocial functioning and affect patients' overall quality of life. A consensus regarding the best patient outcomes to be measur...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3219
更新日期:2011-01-05 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis is an autoimmune arthritis characterized by joint destruction. Anti-citrullinated protein antibodies are pathologic in rheumatoid arthritis, but the role of the citrullinated proteins themselves is much less clear. Citrullination is the conversion of the arginine residues of a protein ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4083
更新日期:2012-11-05 00:00:00
abstract:BACKGROUND:Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with a progressive elevation in pulmonary vascular resistance and subsequent right heart failure and death. Due to unspecific symptoms, the diagnosis of PAH is often delayed. On this basis, it is of great v...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02218-8
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:The SPARCC sacroiliac joint inflammation (SIS) and structural (SSS) scores are reliable measures to quantify abnormalities in the pediatric sacroiliac joint. We aimed to evaluate the utility of online calibration modules for the SIS and SSS and the reliability of their component change scores. METHODS:Chang...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02157-4
更新日期:2020-03-24 00:00:00
abstract:: ...
journal_title:Arthritis research & therapy
pub_type: 信件
doi:10.1186/s13075-018-1766-x
更新日期:2018-12-10 00:00:00
abstract:BACKGROUND:Nitric oxide and prostaglandin E2 (PGE2play pivotal roles in both the pathogenesis of osteoarthritis and catabolic processes in articular cartilage. These mediators are influenced by both IL-1beta and mechanical loading, and involve alterations in the inducible nitric oxide synthase (iNOS) and cyclo-oxygenas...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2389
更新日期:2008-01-01 00:00:00
abstract::Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at the time of conception and anti-phospholipid antibodies are responsi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3227
更新日期:2011-02-25 00:00:00
abstract:INTRODUCTION:The purpose of this study was to examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA). METHODS:Serum levels of anti-cyclic citrullinated...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2945
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Comorbidities may contribute to disease activity and treatment response in rheumatoid arthritis (RA) patients. We defined a somatization comorbidity phenotype (SCP) and examined its influence on response to certolizumab pegol (CZP) using data from the PREDICT trial. METHODS:Patients in PREDICT were randomiz...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-017-1412-z
更新日期:2017-09-29 00:00:00
abstract:INTRODUCTION:Osteoarthritis (OA) is a degenerative disease characterized by cartilage breakdown in the synovial joints. The presence of low-grade inflammation in OA joints is receiving increasing attention, with synovitis shown to be present even in the early stages of the disease. How the synovial inflammation arises ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3555
更新日期:2012-01-08 00:00:00
abstract::Idiopathic CD4 lymphocytopenia (ICL) is a presumed heterogenous syndrome with key element low CD4 T-cell counts (below 300/mm³) without evidence of HIV infection or other known immunodeficiency. The etiology, pathogenesis, and management of ICL remain poorly understood and inadequately defined. The clinical presentati...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4027
更新日期:2012-08-31 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:INTRODUCTION:Standard measurements used to assess murine models of rheumatoid arthritis, notably paw thickness and clinical score, do not align well with certain aspects of disease severity as assessed by histopathology. We tested the hypothesis that non-invasive optical tomographic imaging of molecular biomarkers of i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3038
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patien...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1578-z
更新日期:2018-05-02 00:00:00
abstract:BACKGROUND:Proprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL-receptor (LDLR) which raises LDL-levels. In addition, PCSK9 has proinflammatory immunological effects. Here, we investigate the role of PCSK9 in relation to the inflammatory activity in patients with rheumatoid arthritis (RA). METHODS:PCSK9-le...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02386-7
更新日期:2021-01-19 00:00:00