Abstract:
OBJECTIVE:High serum interferon α (IFNα) activity is a heritable risk factor for systemic lupus erythematosus (SLE). Auto-antibodies found in SLE form immune complexes which can stimulate IFNα production by activating endosomal Toll-like receptors and interferon regulatory factors (IRFs), including IRF5. Genetic variation in IRF5 is associated with SLE susceptibility; however, it is unclear how IRF5 functional genetic elements contribute to human disease. METHODS:1034 patients with SLE and 989 controls of European ancestry, 555 patients with SLE and 679 controls of African-American ancestry, and 73 patients with SLE of South African ancestry were genotyped at IRF5 polymorphisms, which define major haplotypes. Serum IFNα activity was measured using a functional assay. RESULTS:In European ancestry subjects, anti-double-stranded DNA (dsDNA) and anti-Ro antibodies were each associated with different haplotypes characterised by a different combination of functional genetic elements (OR>2.56, p<1.9×10(-14) for both). These IRF5 haplotype-auto-antibody associations strongly predicted higher serum IFNα in patients with SLE and explained >70% of the genetic risk of SLE due to IRF5. In African-American patients with SLE a similar relationship between serology and IFNα was observed, although the previously described European ancestry-risk haplotype was present at admixture proportions in African-American subjects and absent in African patients with SLE. CONCLUSIONS:The authors define a novel risk haplotype of IRF5 that is associated with anti-dsDNA antibodies and show that risk of SLE due to IRF5 genotype is largely dependent upon particular auto-antibodies. This suggests that auto-antibodies are directly pathogenic in human SLE, resulting in increased IFNα in cooperation with particular combinations of IRF5 functional genetic elements. SLE is a systemic autoimmune disorder affecting multiple organ systems including the skin, musculoskeletal, renal and haematopoietic systems. Humoral autoimmunity is a hallmark of SLE, and patients frequently have circulating auto-antibodies directed against dsDNA, as well as RNA binding proteins (RBP). Anti-RBP autoantibodies include antibodies which recognize Ro, La, Smith (anti-Sm), and ribonucleoprotein (anti-nRNP), collectively referred to as anti-retinol-binding protein). Anti-retinol-binding protein and anti-dsDNA auto-antibodies are rare in the healthy population. These auto-antibodies can be present in sera for years preceding the onset of clinical SLE illness and are likely pathogenic in SLE.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Niewold TB,Kelly JA,Kariuki SN,Franek BS,Kumar AA,Kaufman KM,Thomas K,Walker D,Kamp S,Frost JM,Wong AK,Merrill JT,Alarcón-Riquelme ME,Tikly M,Ramsey-Goldman R,Reveille JD,Petri MA,Edberg JC,Kimberly RP,Alarcón GS,doi
10.1136/annrheumdis-2011-200463subject
Has Abstractpub_date
2012-03-01 00:00:00pages
463-8issue
3eissn
0003-4967issn
1468-2060pii
annrheumdis-2011-200463journal_volume
71pub_type
杂志文章abstract:BACKGROUND:To investigate whether patients with primary Sjögren's syndrome (pSS) have an increased tendency to develop other autoimmune diseases. METHODS:A retrospective case note review was carried out on 114 patients in whom a diagnosis of pSS had been made in a department of rheumatology from 1979 onwards. The year...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2004.029066
更新日期:2005-07-01 00:00:00
abstract::A series of observations have led to the hypothesis that normal intestinal microbiota in patients with rheumatoid arthritis may harbour, for genetic reasons, bacteria with cell walls capable of inducing arthritis. Differences occur between bacterial species, and even between strains of a single species, because some c...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.62.9.807
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Whether preradiographic lesions in knees at risk for osteoarthritis are incidental versus disease is unclear. We hypothesised, in persons without but at higher risk for knee osteoarthritis, that: 12-48 month MRI lesion status worsening is associated with 12-48 month incident radiographic osteoarthritis (obje...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-208129
更新日期:2016-09-01 00:00:00
abstract:OBJECTIVES:To further evaluate the role of bacterial antigens in triggering inflammation in the joint in patients with reactive arthritis by studying local antibody synthesis in the joint. METHODS:Yersinia-specific antibodies in paired serum and synovial fluid samples from 29 patients with yersinia triggered reactive ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.53.8.535
更新日期:1994-08-01 00:00:00
abstract:OBJECTIVE:To investigate the prediction of the postpartum onset of rheumatoid arthritis (RA). METHODS:Two thousand five hundred and forty seven healthy pregnant subjects were examined prospectively and the relation between serum rheumatoid factors (RF) and postpartum onset of RA was observed. Rheumatoid factors were m...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.57.8.460
更新日期:1998-08-01 00:00:00
abstract:OBJECTIVE:The expression of antinuclear antibodies (ANA) is considered almost constant in systemic lupus erythematosus (SLE), although recent experience has suggested that many subjects with SLE considered for clinical trials are ANA negative at screening. The objective of this study is to determine whether assay varia...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2017-212599
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Analysis of salivary variables has frequently been proposed as a diagnostic tool for Sjögren's syndrome (SS). Because univocal salivary reference values are lacking, it is currently rather difficult to use sialometry and sialochemistry for diagnosing SS unless major changes have occurred in salivary secretio...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.2.137
更新日期:2002-02-01 00:00:00
abstract:OBJECTIVE:To examine the influence of intravenous pulsed methylprednisolone (MP) on bone mass. METHODS:38 patients (30 women) with various rheumatic disorders requiring intravenous MP pulse treatment were examined at baseline and after 6 months with dual energy x ray absorptiometry (DXA), measuring hip and lumbar spin...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.011734
更新日期:2004-08-01 00:00:00
abstract:OBJECTIVE:Gout, the most common inflammatory arthritis, is associated with premature mortality. Whether this mortality gap has improved over time, as observed in rheumatoid arthritis (RA), is unknown. METHODS:Using an electronic medical record database representative of the UK general population, we identified inciden...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2016-210588
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:Prevalence estimates of rheumatoid arthritis (RA) vary across Europe. Recent estimates in southern European countries showed a lower prevalence than in northern countries. OBJECTIVES:To estimate the prevalence of RA in France in a multiregional representative sample in the year 2001. METHODS:A two stage ra...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2004.029199
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVES:MRI is recommended in the diagnostic process of rheumatoid arthritis (RA) to detect joint damage early. MRI-detected erosions are also present in symptom-free controls, especially at older age. It is unclear if RA-specific MRI-detected erosions can be distinguished from 'physiological' erosions in symptom-fr...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2017-212252
更新日期:2018-06-01 00:00:00
abstract::False positive results were obtained for HIV tests in two men with active systemic lupus erythematosus (SLE) who were suspected of being infected with HIV because of fever, weight loss, lymphadenopathy, and inflammatory myopathy. Enzyme linked immunosorbent assays (ELISAs) for HIV were twice positive when tested three...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.9.1071
更新日期:1992-09-01 00:00:00
abstract::The synovial surface in rabbit knees was examined by scanning electron microscopy (SEM) to define normal surface contour, cell shape, and interstitial exposure. Comparison was made between specimens excised before immersion fixation (I), fixed in situ by vascular perfusion (V) before excision, or fixed in situ under a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.47.3.232
更新日期:1988-03-01 00:00:00
abstract:OBJECTIVE:To investigate the elastic properties of the ascending aorta in untreated patients with giant cell arteritis compared with age and sex matched normal controls. METHODS:Distensibility of the ascending aorta and aortic strain were measured in 22 patients with a recent diagnosis of giant cell arteritis (documen...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2004.021998
更新日期:2005-02-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that pustulosis palmaris et plantaris and psoriatic arthritis (PsA) are two distinct diseases, and that the associated dermatoses are therefore also distinct diseases. METHODS:We prospectively performed clinical, radiological, biological, and bone scan investigations in 23 outpatients ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.55.3.177
更新日期:1996-03-01 00:00:00
abstract:OBJECTIVE:To study immunological markers and compare these markers with standard measures for the clinical and immunological follow up of vasculitis activity in hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis (CV). METHODS:Serial serum samples from eight patients with newly diagnosed HCV associated CV ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.4.385
更新日期:2001-04-01 00:00:00
abstract:OBJECTIVE:To elaborate a clinical practice decision tree for the choice of the first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid arthritis of less than six months' duration. METHODS:Four steps were employed: (1) review of published reports on DMARD efficacy against rheumatoid arthritis; (2) i...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章
doi:10.1136/ard.2005.035436
更新日期:2006-01-01 00:00:00
abstract::T lymphocytes expressing the gamma/delta T cell receptor and B lymphocytes expressing CD5 are known to occur in expanded numbers in the peripheral blood of patients with primary Sjögren's syndrome. The cellular infiltrates for the surface phenotypic markers for alpha/beta and gamma/delta T cell receptors, CD4, CD8, CD...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.50.10.691
更新日期:1991-10-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon gamma (IFNgamma), interleukin 4 (IL4), tumour necrosis factor alpha (TNFalpha), and IL10 at the single cell level in patients with AS in comparison with healthy HL...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.1.36
更新日期:2001-01-01 00:00:00
abstract::Adult human articular cartilage has been maintained in organ culture for 8 days, and the culture medium, which was changed on alternate days, was pooled. Normal and rheumatoid cartilage was obtained from patients and 4 types of culture were prepared: (1) cartilage alone; (2) cartilage + D-penicillamine; (3) cartilage ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.39.1.53
更新日期:1980-02-01 00:00:00
abstract::Superantigens are bacterial, viral, or retroviral proteins which can activate specifically a large proportion of T cells. In contrast with classical peptide antigen recognition, superantigens do not require processing to small peptides but act as complete or partially processed proteins. They can bind to major histoco...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.52.suppl_1.s6
更新日期:1993-03-01 00:00:00
abstract:OBJECTIVE:To determine the serum levels of nucleosome in patients with systemic sclerosis (SSc) and relate the results to the clinical features of SSc. METHODS:Serum nucleosome levels in 91 patients with SSc were examined by ELISA. The expression of Toll-like receptor (TLR) 9 in T and B cells was quantified by flow cy...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-207405
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:We aimed to evaluate the dynamics of treatment response with different composite measures in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial. METHODS:Participants with early disease-modifying antirheumatic drug-naïve psoriatic arthritis (PsA) were randomised 1:1 to either tight...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/annrheumdis-2017-211137
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND:The study aimed to evaluate the use of positron emission tomography/computed tomography (PET/CT) with (68)Ga-PRGD2 as the tracer for imaging of synovial angiogenesis in patients with rheumatoid arthritis (RA). METHODS:Twenty untreated active patients with RA underwent (68)Ga-PRGD2 PET/CT and (18)F-FDG PET/C...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204820
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:To elucidate factors involved in the arthritogenicity of bacterial cell walls. METHODS:For characterisation of an arthritogenic Eubacterium aerofaciens cell wall, peptidoglycan-polysaccharide (PG-PS) polymers were isolated by removing cell wall associated proteins (CWPs), PG and PS moieties were separated, a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.3.269
更新日期:2001-03-01 00:00:00
abstract:OBJECTIVES:To compare the effects of etanercept (ETN) 50 mg once weekly plus methotrexate (MTX) versus MTX alone on patient-reported outcomes (PROs) and the relationship between remission and PRO improvement. METHODS:In this double-blind, randomised clinical trial (COMET), PROs included: the Health Assessment Question...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/ard.2008.102509
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVES:Leri's pleonosteosis (LP) is an autosomal dominant rheumatic condition characterised by flexion contractures of the interphalangeal joints, limited motion of multiple joints, and short broad metacarpals, metatarsals and phalanges. Scleroderma-like skin thickening can be seen in some individuals with LP. We u...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204309
更新日期:2015-06-01 00:00:00
abstract::HLA types, especially HLA-DR3, are associated with the development of toxic reactions in patients with rheumatoid arthritis after treatment with gold or D-penicillamine. In this study, after treatment with sulphasalazine, leucopenia was observed in three patients, who all had a history of leucopenia after previous gol...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.48.7.539
更新日期:1989-07-01 00:00:00
abstract:OBJECTIVES:To describe presentation and outcome of patients with scleroderma renal crisis (SRC). METHODS:SRC was defined as rapidly progressive oliguric renal insufficiency and/or rapidly progressive arterial hypertension occurring during the course of systemic sclerosis (SSc). Chronic dialysis-free survival was analy...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2006.066985
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVE:We sought to determine histologic and gene expression features of clinical improvement in early diffuse cutaneous systemic sclerosis (dcSSc; scleroderma). METHODS:Fifty-eight forearm biopsies were evaluated from 26 individuals with dcSSc in two clinical trials. Histologic/immunophenotypic assessments of glob...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2020-217840
更新日期:2021-02-01 00:00:00