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 within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients. METHODS:Dermal interstitial fluid sample from the involved forearm skin, and synchronous plasma samples were collected from SSc patients (n = 26, diffuse cutaneous SSc (DcSSc) n = 20, limited cutaneous SSc (LcSSc) n = 6), and healthy controls (HC) (n = 10) and profiled by Luminex® array for inflammatory cytokines, chemokines, and growth factors. RESULTS:Luminex® profiling of the dermal blister fluid showed increased inflammatory cytokines (median interleukin ( IL)-6 in SSc 39.78 pg/ml, HC 5.51 pg/ml, p = 0.01, median IL-15 in SSc 6.27 pg/ml, HC 4.38 pg/ml, p = 0.03), chemokines (monocyte chemotactic protein (MCP)-3 9.81 pg/ml in SSc, 7.18 pg/ml HC, p = 0.04), and profibrotic growth factors (platelet derived growth factor (PDGF)-AA 10.38 pg/ml versus 6.94 pg/ml in HC, p = 0.03). In general dermal fluid and plasma cytokine levels did not correlate, consistent with predominantly local production of these factors within the dermal lesions, rather than leakage from the serum. In hierarchical clustering and network analysis IL-6 emerged as a key central mediator. CONCLUSIONS:Our data confirm that an immuno-inflammatory environment and aberrant vascular repair are intimately linked to fibroblast activation in lesional skin in SSc. This non-invasive method could be used to profile disease activity in the clinic, and identifies key inflammatory or pro-fibrotic proteins that might be targeted therapeutically. Distinct subgroups of SSc may be defined that show innate or adaptive immune cytokine signatures.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Clark KE,Lopez H,Abdi BA,Guerra SG,Shiwen X,Khan K,Etomi O,Martin GR,Abraham DJ,Denton CP,Stratton RJdoi
10.1186/s13075-015-0575-8subject
Has Abstractpub_date
2015-03-23 00:00:00pages
73eissn
1478-6354issn
1478-6362pii
10.1186/s13075-015-0575-8journal_volume
17pub_type
杂志文章abstract:BACKGROUND:The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are included in the 2010 classification criteria for rheumatoid arthritis (RA). However, a considerable number of RA pa...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1591-2
更新日期:2018-05-03 00:00:00
abstract:INTRODUCTION:Semaphorin 3A (sema3A) and neuropilin-1 (NP-1) play a regulatory role in immune responses and have a demonstrated effect on the course of collagen induced arthritis. This study was undertaken to evaluate the role of sema3A and NP-1 in the pathogenesis of systemic lupus erythematosus (SLE) and the specific ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3881
更新日期:2012-06-14 00:00:00
abstract:INTRODUCTION:Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0531-7
更新日期:2015-03-05 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:Fibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades adjacent cartilage and bone in rheumatoid arthritis (RA). The study was undertaken to determine the effect of interleukin-17 (IL-17) on the survival and/or proliferation of FLSs from RA patients and to investigate wh...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4179
更新日期:2013-02-20 00:00:00
abstract::The characteristics of rheumatoid arthritis (RA) pathology include the infiltration of inflammatory leukocytes, the proliferation of synovial cells, and the presence of extensive angiogenesis, referred to as rheumatoid pannus. Fas ligand is critical to the homeostatic regulation of the immune response, but its role in...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2181
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:The high-affinity receptor for IgG Fcgamma/CD64 is critical for the development of lupus nephritis (LN). Cross-linking Fc receptor on recruited monocytes by IgG-containing immune complexes is a key step in immune-complex-mediated nephritis in systemic lupus erythematosus (SLE). The goal of this study was t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2590
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus is a chronic autoimmune disease characterized by an abundance of autoantibodies against nuclear antigens. Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PC...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4086
更新日期:2012-11-08 00:00:00
abstract::Following publication of the original article [1], the authors reported a typesetting error. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13075-018-1753-2
更新日期:2018-11-05 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: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:Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necros...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4558
更新日期:2014-05-07 00:00:00
abstract:INTRODUCTION:The objective of this study is to determine if multiple systemic autoimmune diseases (SAID) share gene expression pathways that could provide insights into pathogenic mechanisms common to these disorders. METHODS:RNA microarray analyses (Agilent Human 1A(V2) 20K oligo arrays) were used to quantify gene ex...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3330
更新日期:2011-04-26 00:00:00
abstract::The characteristic of a biomarker that makes it a useful surrogate is the ability to identify a high risk of clinically important benefits or harms occurring in the future. A number of definitions or descriptions of surrogate definition have been put forward. Most recently the Institute of Medicine of the National Aca...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4176
更新日期:2013-01-01 00:00:00
abstract::Decreased number and impaired functions of endothelial progenitor cells (EPCs) leading to impaired vasculogenesis have been associated with rheumatoid arthritis (RA). Defective vasculogenesis has also been implicated in premature atherosclerosis in RA. Recently, early-outgrowth monocytic and late-outgrowth hemangiobla...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2943
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Autoreactive B cells are crucial players in the pathogenesis of rheumatoid arthritis (RA). Autoantibodies specific for citrullinated proteins (ACPA), present in the serum of approximately 60-70 % of patients, have a pathogenic role in the disease. B cell depleting therapies may result in a transient immunosu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0918-0
更新日期:2016-01-16 00:00:00
abstract:INTRODUCTION:Cell therapy is a rapidly growing area of research for the treatment of osteoarthritis (OA). This work is aimed to investigate the efficacy of intra-articular adipose-derived stromal cell (ASC) injection in the healing process on cartilage, synovial membrane and menisci in an experimental rabbit model. ME...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4156
更新日期:2013-01-29 00:00:00
abstract:BACKGROUND:Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1128-5
更新日期:2016-10-06 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis (RA) is a chronic inflammatory and destructive disease of the joint. The synovial lining consists of two main types of cells: synovial fibroblasts and macrophages. The macrophage-derived cytokine TNFα stimulates RA synovial fibroblasts to proliferate and produce growth factors, chemoki...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3778
更新日期:2012-03-14 00:00:00
abstract:INTRODUCTION:Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3792
更新日期:2012-04-02 00:00:00
abstract:INTRODUCTION:Studies in the spontaneous ankylosis model in aging male DBA/1 mice and in patients with ankylosing spondylitis provide evidence that inflammation and new tissue formation leading to joint or spine ankylosis are likely linked but largely uncoupled processes. We previously proposed the 'entheseal stress' hy...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3772
更新日期:2012-03-12 00:00:00
abstract:INTRODUCTION:The aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis. METHODS:Serum levels of S100A4 were determined in 43 dermatomyositis (DM), 39 polymyositis (PM) and 22 cancer associated myositis (CAM) patients as well as in 77 healthy co...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0468-2
更新日期:2014-10-31 00:00:00
abstract::Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis. In order to characterize the temp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1458
更新日期:2005-01-01 00:00:00
abstract::In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1737
更新日期:2005-01-01 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:Rheumatoid arthritis (RA) and periodontitis (PD) have been suggested to share many clinical and pathological features. However, few reports have investigated the relationship between the degree of PD and the treatment response to RA. This study aimed to examine the relationship between the extent of PD and t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02269-x
更新日期:2020-07-25 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::As a consequence of the avascular nature of cartilage the microenvironment in which chondrocytes must exist is characterized by hostile conditions, most prominently very low levels of oxygen (hypoxia). In recent years, a vast number of papers reporting on the role of hypoxia in cartilage development and disease has be...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar1894
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:The patient's perspective is becoming increasingly important in clinical and policy decisions. In this study, we aimed to evaluate the preferences of patients with, or at risk of, osteoporosis for medication attributes, and to establish how patients trade between these attributes. METHODS:A discrete choic...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4465
更新日期:2014-01-31 00:00:00
abstract::The autoinflammatory diseases, also known as periodic fever syndromes, are disorders of innate immunity which can be inherited or acquired and which cause recurrent, self-limiting, seemingly spontaneous episodes of systemic inflammation and fever in the absence of autoantibody production or infection. There has been m...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2579
更新日期:2009-01-01 00:00:00