Abstract:
INTRODUCTION:Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serves as a helpful discriminator in genetic studies and today anti-citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic contributor for the risk of RA, but is not sufficient to drive autoimmunity and additional genetic and environmental factors are involved. Hence, we addressed the association of previously discovered RA loci with disease-specific autoantibody responses in RA patients stratified by HLA-DRB1*04. METHODS:We investigated 2178 patients from three RA cohorts from Sweden and Spain for 41 genetic variants and four autoantibodies, including the generic anti-CCP as well as specific responses towards citrullinated peptides from vimentin, alpha-enolase and type II collagen. RESULTS:Our data demonstrated different genetic associations of autoantibody-positive disease subgroups in relation to the presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were identified. The SNP in PTPN22 was associated with presence of anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel test P = 0.0001, P corrected <0.05), whereas SNPs in CDK6 and PADI4 were associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel-Haenszel test P = 0.0004, P corrected <0.05 for both markers). Additionally we see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02). CONCLUSION:These data point to alternative pathways for disease development in clinically similar RA subgroups and suggest an approach for study of genetic complexity of disease with strong contribution of HLA.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Snir O,Gomez-Cabrero D,Montes A,Perez-Pampin E,Gómez-Reino JJ,Seddighzadeh M,Klich KU,Israelsson L,Ding B,Catrina AI,Holmdahl R,Alfredsson L,Klareskog L,Tegnér J,Gonzalez A,Malmström V,Padyukov Ldoi
10.1186/s13075-014-0414-3subject
Has Abstractpub_date
2014-08-20 00:00:00pages
414issue
4eissn
1478-6354issn
1478-6362pii
s13075-014-0414-3journal_volume
16pub_type
杂志文章abstract:INTRODUCTION:Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2992
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JI...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02279-9
更新日期:2020-08-12 00:00:00
abstract:INTRODUCTION:We aimed to understand the changes in cartilage lubricin expression and immunolocalisation in responsed to treadmill running with different intensities in a rat model. METHODS:A total of 24 male Wistar rats were randomly assigned into groups of control (CON), low-intensity running (LIR), moderate-intensit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4101
更新日期:2012-11-24 00:00:00
abstract:BACKGROUND:In osteoarthritis, chondrocytes adopt an abnormal hypertrophic morphology and upregulate the expression of the extracellular matrix-degrading enzymes, MMP-13 and ADAMTS-5. The activation of the hedgehog signalling pathway has been established in osteoarthritis and is thought to influence both of these proces...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0891-z
更新日期:2015-12-24 00:00:00
abstract::The present studies were initiated to determine the protein expression patterns of fibroblast-like synovial (FLS) cells derived from the synovia of rheumatoid arthritis patients. The cellular proteins were separated by two-dimensional polyacrylamide gel electrophoresis and the in-gel digested proteins were analyzed by...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1153
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue fr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4157
更新日期:2013-01-29 00:00:00
abstract:INTRODUCTION:Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have be...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/s13075-014-0507-z
更新日期:2014-12-14 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: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:BACKGROUND:To analyze whether ANA-positive idiopathic anterior uveitis differs from JIA-associated uveitis concerning clinical course, response to treatment, and disease outcome. METHODS:Prospective study of the National Paediatric Rheumatological Database (NPRD) including its uveitis add-on module from the years 2002...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02166-3
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:The aim was to further characterize immunoglobulin G4-related disease (IgG4-RD) by a large-scale multicenter study of its clinical and laboratory features conducted by multidisciplinary physicians of IgG4-RD in Japan. METHODS:Various specialists retrospectively evaluated IgG4-RD patients diagnosed between 1...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-017-1467-x
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND:Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disea...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析
doi:10.1186/s13075-018-1604-1
更新日期:2018-05-30 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:Osteoclastogenesis plays an important role in the bone erosion of rheumatoid arthritis (RA). Recently, Notch receptors have been implicated in the development of osteoclasts. However, the responsible Notch ligands have not been identified yet. This study was undertaken to determine the role of individual N...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3758
更新日期:2012-03-05 00:00:00
abstract::Chemokines play an essential role in the progression of rheumatoid arthritis (RA). In the present study we examined the expression and regulatory mechanisms of IFN-gamma inducible protein (IP)-10 in RA synovitis. RA synovial fluid contained greater amounts of IP-10 than did synovial fluid from patients with osteoarthr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar616
更新日期:2003-01-01 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:INTRODUCTION:Excess C/EBP homologous protein (CHOP) expression is one feature of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress. Here, we focused on CHOP expression and function in chondrocytes. METHODS:We studied human knee osteoarthritis (OA) cartilage, bovine chondrocytes cultured in algin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4415
更新日期:2013-01-01 00:00:00
abstract::Human T cell leukaemia virus type I (HTLV-I) is known to be involved in late-onset chronic polyarthritis as HTLV-I-associated arthropathy. However, it is unclear whether HTLV-I infection could modify the pathophysiology of osteoarthritis (OA). In this study we compared several inflammatory cytokines, such as C-termina...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1193
更新日期:2004-01-01 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: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: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: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...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3205
更新日期:2010-01-01 00:00:00
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:BACKGROUND:African Americans with systemic lupus erythematosus (SLE) have increased renal disease compared to Caucasians, but differences in other comorbidities have not been well-described. We used an electronic health record (EHR) technique to test for differences in comorbidities in African Americans compared to Cau...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1561-8
更新日期:2018-04-10 00:00:00
abstract:BACKGROUND:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02324-7
更新日期:2020-10-15 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::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:BACKGROUND:Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of se...
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/s13075-018-1610-3
更新日期:2018-06-07 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies and immune complex deposition in various organs. Aberrations in the T lymphocyte compartment and dysregulated cytokine production are key features of SLE pathogenesis and disease progression. Recently...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3194
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Sarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skel...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13075-018-1786-6
更新日期:2018-12-27 00:00:00