Abstract:
BACKGROUND:Pepsin agglutinators, discovered over 50 years ago, have been recently referred to as anti-hinge antibodies (AHAs) because of their reaction with the IgG hinge epitope. AHAs have different reactivity for each hinge epitope generated by each protease that cleaves the hinge region at different sites. Moreover, AHAs have different reactivity against different hinge epitopes derived from each IgG subclass even when the same protease is used. Since the expression of matrix metalloproteinase-3 (MMP-3) is enhanced in rheumatoid arthritis (RA), AHA production could also be increased. The purpose of this study was to determine whether the levels of AHAs against IgG hinge epitopes produced by MMP-3 are elevated in RA. METHODS:The serum levels of IgG or IgA AHAs against the IgG1/IgG4 F(ab')2 fragments, generated by either MMP-3 or pepsin, were measured using ELISA in 111 patients with RA and 81 healthy controls (HC). Receiver operating characteristic (ROC) analysis was used for obtaining optimal cutoff values and cutoff values indicating high specificity (> 95%) of the AHA. The targeted epitope of a specific AHA was investigated through inhibition ELISA. RESULTS:Seven AHAs were statistically higher in RA patients than in HC, except IgG AHA against IgG1 F(ab')2, which was generated by MMP-3 proteolytic cleavage. The areas under the ROC curve were 0.66-0.80, although the sensitivities at high specificity were low (5.4-24.3%). The cumulative number of positive AHAs in each individual was statistically higher in RA patients than in HC, suggesting the extreme extent of AHA repertoires in RA. Inhibition studies revealed that IgG AHAs against IgG4 F(ab')2 fragments generated by pepsin cross-reacted with IgG1 F(ab')2 fragments generated by pepsin. Multivariate logistic regression analysis identified the IgG AHA against IgG4 F(ab')2 fragments generated by pepsin as an independent variable for RA diagnosis, even in RA patients who were negative for both RF and ACPA (odds ratio 1.18, 95% CI 1.06-1.32; P = 0.003). Additional experiments using non-RA patients finally strengthened the diagnostic utility. CONCLUSION:In RA patients, we observed diversification and amplification of AHA repertoires and diagnostic utility of the specific AHA against IgG4 F(ab')2 fragments generated by pepsin but not MMP-3.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Ota T,Ota SI,Uchino A,Nagano Sdoi
10.1186/s13075-020-02251-7subject
Has Abstractpub_date
2020-06-26 00:00:00pages
161issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-020-02251-7journal_volume
22pub_type
杂志文章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::Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and duri...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1863
更新日期:2006-01-01 00:00:00
abstract::Lupus nephritis is a major contributor to morbidity and mortality in systemic lupus erythematosus, but little is known about the pathogenic processes that underlie the progressive decay in renal function. A common finding in lupus nephritis is thickening of glomerular basement membranes associated with immune complex ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2532
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term stru...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2043-3
更新日期:2019-12-04 00:00:00
abstract::Synovial biomarker analysis in rheumatoid arthritis can be used to evaluate drug effect in clinical trials of novel therapeutic agents. Previous studies of synovial gene expression for these studies have mainly relied on histological methods including immunohistochemistry and in situ hybridization. To increase the rel...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1004
更新日期:2003-01-01 00:00:00
abstract::Scleroderma (systemic sclerosis; SSc) is characterised by fibrosis of the skin and internal organs in the context of autoimmunity and vascular perturbation. Overproduction of extracellular matrix components and loss of specialised epithelial structures are analogous to the process of scar formation after tissue injury...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4230
更新日期:2013-01-01 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:INTRODUCTION:Patients with rheumatoid arthritis (RA) are at an increased risk of malignancies compared with the general population. This has raised concerns regarding these patients, particularly with the widespread use of immunomodulating therapies, including biologic disease-modifying antirheumatic drugs (DMARDs). We...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s13075-015-0728-9
更新日期:2015-08-15 00:00:00
abstract::A considerable amount of research time has been invested in studies aimed at elucidating pathogenic processes in systemic sclerosis (SSc). Despite this, major challenges for biomedical science remain, such as identification of the key factors that determine susceptibility to SSc, and elucidation of the precise nature ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2186
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to examine data from the Johnston County Osteoarthritis (OA) Project for independent associations of educational attainment, occupation and community poverty with tibiofemoral knee OA. METHODS:A cross-sectional analysis was conducted on 3,591 individuals (66% Caucasian and 34...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3492
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Low-intensity pulsed ultrasound (LIPUS) has been known to promote bone healing by nonthermal effects. In recent studies, LIPUS has been shown to reduce inflammation in injured soft tissues. Xerostomia is one of the most common symptoms in Sjögren syndrome (SS). It is caused by a decrease in the quantity or...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0798-8
更新日期:2015-10-07 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate cau...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3759
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:Despite growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was to detect the levels of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0632-3
更新日期:2015-05-21 00:00:00
abstract:BACKGROUND:In some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement ('hypocomplementaemia') is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1147-2
更新日期:2016-10-22 00:00:00
abstract::There is increasing recognition that central pain sensitivity plays an important role in pain severity among patients with osteoarthritis. Murphy and colleagues identified clusters of patients with osteoarthritis according to pain severity and accompanying symptoms, and one of these groups appeared to have a greater d...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3499
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody® with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum a...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0651-0
更新日期:2015-05-20 00:00:00
abstract::Genetic and environmental factors may play a role in the etiopathology of fibromyalgia syndrome (FMS) and other related syndromes. There is a high aggregation of FMS in families of FMS patients. The mode of inheritance is unknown but it is most probably polygenic. There is evidence that polymorphisms of genes in the s...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2005
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13075-019-2014-8
更新日期:2019-11-13 00:00:00
abstract:BACKGROUND:The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relationship between autoantib...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1061-7
更新日期:2016-07-07 00:00:00
abstract:INTRODUCTION:Though remission is currently a treatment goal in patients with rheumatoid arthritis (RA), the number of patients who achieve and sustain remission in daily practice is still small. It is suggested that early remission will be associated with sustainability of remission. The aim was to study the associatio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3027
更新日期:2010-01-01 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:OBJECTIVES:Blau syndrome (BS) is a rare dominantly inherited autoinflammatory disorder associated with mutations in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Biologic therapy of BS yielded diverse results. We aimed to evaluate clinical features and outcomes of Chinese patients with BS who ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13075-019-2017-5
更新日期:2019-11-12 00:00:00
abstract:INTRODUCTION:Notable weakness of the quadriceps muscles is typically observed as a consequence of knee joint arthritis, knee surgery and knee injury. This is partly due to ongoing neural inhibition that prevents the central nervous system from fully activating the quadriceps, a process known as arthrogenic muscle inhib...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0724-0
更新日期:2015-08-12 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a me...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1122-y
更新日期:2016-10-06 00:00:00
abstract::One in six patients with systemic sclerosis will develop pulmonary arterial hypertension (PAH). Screening with echocardiography and possibly pulmonary function testing (to determine the diffusing capacity of carbon monoxide) is recommended to detect PAH at a less severe stage. However, real-world screening programs ha...
journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/s13075-017-1347-4
更新日期:2017-06-06 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:IL-10 is a very important anti-inflammatory cytokine. However, the role of this cytokine in T cells in the pathogenesis of collagen-induced arthritis is unclear. The purpose of this study was to define the role of IL-10 signaling in T cells in the pathogenesis of collagen-induced arthritis. METHODS:IL-10 ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3545
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Lack of adequate self-care, frequent admissions, and poor quality of life are common and serious problems in adult patients with systemic lupus erythematosus (SLE). Some studies have revealed that transitional care is effective in improving self-care and quality of life as well as reducing rehospitalization ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-018-1670-4
更新日期:2018-08-16 00:00:00
abstract:BACKGROUND:Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. There is a need for bio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1040-z
更新日期:2016-06-16 00:00:00
abstract:BACKGROUND:Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2018-4
更新日期:2019-11-27 00:00:00