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 disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. METHODS:We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. RESULTS:We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10- 8): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10- 6), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10- 5), interleukin-4 signaling (p = 3.97 × 10- 5) and cell surface interactions at the vascular wall (p = 4.63 × 10- 5). CONCLUSIONS:Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Julià A,López-Longo FJ,Pérez Venegas JJ,Bonàs-Guarch S,Olivé À,Andreu JL,Aguirre-Zamorano MÁ,Vela P,Nolla JM,de la Fuente JLM,Zea A,Pego-Reigosa JM,Freire M,Díez E,Rodríguez-Almaraz E,Carreira P,Blanco R,Taboada VM,Lódoi
10.1186/s13075-018-1604-1subject
Has Abstractpub_date
2018-05-30 00:00:00pages
100issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-018-1604-1journal_volume
20pub_type
杂志文章,meta分析abstract:INTRODUCTION:Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruct...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4474
更新日期:2014-02-05 00:00:00
abstract::Patients with lupus have a continuous production of IFNα and display an increased expression of IFNα-regulated genes. The reason for the ongoing IFNα synthesis in these patients seems to be an activation of plasmacytoid dendritic cells (pDCs) by immune complexes (ICs), consisting of autoantibodies in combination with ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2884
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS). ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3823
更新日期:2012-04-30 00:00:00
abstract::The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar2322
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Autoantibodies against mutated and citrullinated vimentin (MCV) represent a novel diagnostic marker for rheumatoid arthritis (RA). Recently, an increased sensitivity for anti-MCV compared to autoantibodies against cyclic citrullinated peptides (anti-CCP2) was shown in cohorts of patients with early RA and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3057
更新日期:2010-01-01 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:INTRODUCTION:We previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used to target anti-inflammatory therapeutics specifically to inflamed arthritic joints. The objective of the present study was to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4613
更新日期:2014-07-16 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:BACKGROUND:To investigate the association between knee pain and risk factors including low back pain and to develop a score to predict new knee pain in an older population, using population-based longitudinal cohort data. METHODS:We collected a questionnaire on self-reported knee pain and demographic data in a systema...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1884-0
更新日期:2019-04-15 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:INTRODUCTION:The objective was to study immune regulation in a mouse model of rheumatoid arthritis that exhibits considerable heterogeneity of disease activity. METHODS:T-cell receptor transgenic mice, in which nearly all CD4+ T cells recognize a single peptide of type II collagen, were immunized with collagen and obs...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2795
更新日期:2009-01-01 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: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,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02251-7
更新日期:2020-06-26 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::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::In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1772
更新日期:2005-01-01 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::Over the last decades, genetic factors for rheumatoid diseases like the HLA haplotypes have been studied extensively. However, during the past years of research, it has become more and more evident that the influence of epigenetic processes on the development of rheumatic diseases is probably as strong as the genetic ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2500
更新日期:2008-01-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyperreactivity. The underlying causes of the diffuse B-cell over-reactivity are unclear, but potential candidates include (a) intrinsic hyper-reactivity leading to polyclonal B-cell activation wit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3433
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:To aim was to investigate the additional value of incorporating the de Vlam cervical facet joint score in the modified ankylosing spondylitis (AS) spine score (mSASSS) for the evaluation of spinal radiographic outcome in AS. METHOD:Baseline and 4-year radiographs from 98 consecutive patients from the Gronin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1285-1
更新日期:2017-04-26 00:00:00
abstract:BACKGROUND:In this study, we evaluated the impact of obesity and/or overweight on the achievement of minimal disease activity (MDA) in patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) receiving an anti-rheumatic treatment. Obesity can be considered a low-grade, chronic systemic inflam...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s13075-016-1194-8
更新日期:2016-12-13 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:BACKGROUND:Final data are presented for the ORAL Sequel long-term extension (LTE) study evaluating the safety and efficacy of tofacitinib 5 mg and 10 mg twice daily (BID) for up to 9.5 years in patients with rheumatoid arthritis (RA). METHODS:Eligible patients had previously completed a phase 1, 2, or 3 qualifying ind...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/s13075-019-1866-2
更新日期:2019-04-05 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: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:BoneXpert (BX) is a newly developed medical device based on digital X-ray radiogrammetry to measure human cortical bone thickness. The aim of this study was to quantify cortical bone loss of the metacarpals in patients with psoriatic arthritis (PsA) and compare these findings with other radiological scoring ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1145-4
更新日期:2016-10-25 00:00:00
abstract:INTRODUCTION:The important functions of the meniscus are shock absorption, passive stabilization and load transmission of the knee. Because of the avascularity of two-thirds of the meniscal center region, the treatment of tears in this area is hard. Recently, microRNAs have been proven to play an important role in the ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0488-y
更新日期:2014-11-28 00:00:00
abstract:INTRODUCTION:The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse. METHODS:The prooxidative, antiproliferative, and cytotoxic effects...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4351
更新日期:2013-10-28 00:00:00
abstract:BACKGROUND:Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. METHOD:Assessm...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-019-2055-z
更新日期:2019-12-04 00:00:00
abstract::Memory T cells display phenotypic heterogeneity. Surface antigens previously regarded as exclusive markers of naive T cells, such as L-selectin (CD62L), can also be detected on some memory T cells. Moreover, a fraction of CD45RO+ (positive for the short human isoform of CD45) memory T cells reverts to the CD45RA+ (pos...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar610
更新日期:2003-01-01 00:00:00