Abstract:
INTRODUCTION:Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using a new methodology. METHODS:Human fibrinogen was citrullinated in vitro by peptidylarginine deiminases (PAD), subjected to proteolysis and the resulting peptides were fractionated by ion exchange chromatography. The peptide composition of the citrullinated peptide-containing fractions was determined by high resolution tandem mass spectrometry. The recognition of these fractions by patient sera was subsequently analyzed by imaging surface plasmon resonance on microarrays. RESULTS:In total about two-thirds of the 81 arginines of human fibrinogen were found to be susceptible to citrullination by the human PAD2, the human PAD4 or the rabbit PAD2 enzymes. Citrullination sites were found in all three polypeptide chains of fibrinogen, although the α-chain appeared to contain most of them. The analysis of 98 anti-citrullinated protein antibody-positive RA sera using the new methodology allowed the identification of three major citrullinated epitope regions in human fibrinogen, two in the α- and one in the β-chain. CONCLUSIONS:A comprehensive overview of citrullination sites in human fibrinogen was generated. The multiplex analysis of peptide fractions derived from a post-translationally modified protein, characterized by mass spectrometry, with patient sera provides a versatile system for mapping modified amino acid-containing epitopes. The citrullinated epitopes of human fibrinogen most efficiently recognized by RA autoantibodies are confined to three regions of its polypeptides.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
van Beers JJ,Raijmakers R,Alexander LE,Stammen-Vogelzangs J,Lokate AM,Heck AJ,Schasfoort RB,Pruijn GJdoi
10.1186/ar3205subject
Has Abstractpub_date
2010-01-01 00:00:00pages
R219issue
6eissn
1478-6354issn
1478-6362pii
ar3205journal_volume
12pub_type
杂志文章abstract:BACKGROUND:Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02361-2
更新日期:2020-11-09 00:00:00
abstract:INTRODUCTION:Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0865-1
更新日期:2015-12-05 00:00:00
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:We sought to assess vascularity in wrist tenosynovitis by using power Doppler ultrasound (PDUS) and to compare detection of intra- and peritendinous vascularity with that of contrast-enhanced grey-scale ultrasound (CEUS). METHODS:Twenty-six tendons of 24 patients (nine men, 15 women; mean age ± SD, 54.4 ±...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3185
更新日期:2010-01-01 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: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:BACKGROUND:In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages (MHEs) and microthromboses (MTs), observed in nailfold videocapillaroscopy was a good indicator of the steady state level of disease activity (DA) in patients with systemic sclerosis (SSc) when the Europ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2032-6
更新日期:2019-11-29 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: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::Behçet's disease is characterized by recurrent aphthous stomatitis, uveitis, genital ulcers, and skin lesions. The role of the HLA-B*51 gene has been confirmed in recent years, although its contribution to the overall genetic susceptibility to Behçet's disease was estimated to be only 19%. The production of a variety ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar757
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Monosodium urate monohydrate (MSU) crystals synergize with various toll-like receptor (TLR) ligands to induce cytokine production via activation of the NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLPR3) inflammasome. This has been demonstrated in vitro using human cell lines or monocytes of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3898
更新日期:2012-07-04 00:00:00
abstract:BACKGROUND:The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). METHODS:Serum from patients with RA and osteoarthritis (OA), and healthy controls, and synov...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02315-8
更新日期:2020-09-23 00:00:00
abstract:INTRODUCTION:Ankylosing spondylitis (AS) is an inflammatory disease associated with new bone formation and an increased risk of osteoporosis and fractures. The negative effects of AS on bone microarchitecture and strength are unclear. Thus, we conducted an observational study to analyze the effect of AS on bone microar...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0873-1
更新日期:2015-12-24 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::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
abstract:INTRODUCTION:Bone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs. METHODS:In total, 394 older men and women (mean age, 63 years; range, 52 ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3689
更新日期:2012-01-18 00:00:00
abstract:BACKGROUND:RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0982-5
更新日期:2016-04-12 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:INTRODUCTION:BRAF (v raf murine sarcoma viral oncogene homologue B1) is a serine-threonine kinase involved in the mitogen-activated protein kinase (MAPK) signalling pathway, known to be implicated in the production of pro-inflammatory cytokines.We have observed that sera from rheumatoid arthritis (RA) patients recogniz...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3165
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we repo...
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/ar2948
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-2133-2
更新日期:2020-03-27 00:00:00
abstract:INTRODUCTION:Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology appr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4081
更新日期:2012-11-01 00:00:00
abstract::A growing body of literature has demonstrated that the multifunctional glycoprotein osteopontin (OPN), has a role in type I interferon (IFN) production and may be involved in systemic lupus erythematosus (SLE) pathogenesis. A recent report has provided further support for this, demonstrating an association between rai...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar4172
更新日期:2013-03-08 00:00:00
abstract::Susceptibility for giant cell arteritis increases with chronological age, in parallel with age-related restructuring of the immune system and age-induced remodeling of the vascular wall. Immunosenescence results in shrinkage of the naïve T-cell pool, contraction of T-cell diversity, and impairment of innate immunity. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3358
更新日期:2011-08-02 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: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: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::Autoantibodies to neutrophil cytoplasmic antigen-associated vasculitis (AAV) is characterised by inflammation of blood vessels. The introduction of immunosuppressive therapy with glucocorticoids and cyclophosphamide transformed AAV from a fatal condition to a largely treatable condition. Over the past 30 years, consid...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3797
更新日期:2012-04-30 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:BACKGROUND:Osteoarthritis (OA) is a whole joint disease that affects all joint tissues, with changes in the articular cartilage (AC), subchondral bone and synovium. Pathologies in menisci and ligaments, however, are rarely analysed, although both are known to play vital roles in the mechanical stability of the joint. T...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02261-5
更新日期:2020-07-16 00:00:00