Abstract:
OBJECTIVES:To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis. METHODS:Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated renal biopsies were obtained at time of diagnosis and microdissected into glomerular and tubulointerstitial compartments. Microarray-derived differential gene expression of 88 genes representing critical enzymes of metabolic pathways and 25 genes related to immune cell markers was compared between disease groups. Correlation analyses measured relationships between metabolic pathways, kidney function and cytokine production. RESULTS:Reduced steady state levels of mRNA species were enriched in pathways of oxidative phosphorylation and increased in the pentose phosphate pathway (PPP) with maximal perturbation in AAV and SLE followed by NS, and least in LD. Transcript regulation was isozymes specific with robust regulation in hexokinases, enolases and glucose transporters. Intercorrelation networks were observed between enzymes of the PPP (eg, transketolase) and macrophage markers (eg, CD68) (r=0.49, p<0.01). Increased PPP transcript levels were associated with reduced glomerular filtration rate in the glomerular (r=-0.49, p<0.01) and tubulointerstitial (r=-0.41, p<0.01) compartments. PPP expression and tumour necrosis factor activation were tightly co-expressed (r=0.70, p<0.01). CONCLUSION:This study demonstrated concordant alterations of the renal transcriptome consistent with metabolic reprogramming across different forms of glomerulonephritis. Activation of the PPP was tightly linked with intrarenal macrophage marker expression, reduced kidney function and increased production of cytokines. Modulation of glucose metabolism may offer novel immune-modulatory therapeutic approaches in rare kidney diseases.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Grayson PC,Eddy S,Taroni JN,Lightfoot YL,Mariani L,Parikh H,Lindenmeyer MT,Ju W,Greene CS,Godfrey B,Cohen CD,Krischer J,Kretzler M,Merkel PA,Vasculitis Clinical Research Consortium, the European Renal cDNA Bank cohort, and thdoi
10.1136/annrheumdis-2017-212935subject
Has Abstractpub_date
2018-08-01 00:00:00pages
1226-1233issue
8eissn
0003-4967issn
1468-2060pii
annrheumdis-2017-212935journal_volume
77pub_type
杂志文章abstract:BACKGROUND:Small studies have linked α1 antitrypsin (α1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). OBJECTIVE:To test the validity and the mechanism of this association between α1AT and AAV. METHODS:The distribution of α1AT deficiency alleles Z and S was co...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2011.153569
更新日期:2011-10-01 00:00:00
abstract::A patient with systemic lupus erythematosus who developed pneumococcal epiglottitis is described and the literature reviewed. This infection is extremely rare in adults, and only 10 cases, none of them with SLE, have so far been reported. Epiglottitis is usually caused by Haemophilus influenzae. However, in immunocomp...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.41.6.615
更新日期:1982-12-01 00:00:00
abstract:OBJECTIVE:To perform a prospective long term follow up study comparing conventional radiography (CR), ultrasonography (US), and magnetic resonance imaging (MRI) in the detection of bone erosions and synovitis in rheumatoid arthritis (RA) finger joints. METHODS:The metacarpophalangeal and proximal interphalangeal joint...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.041814
更新日期:2006-05-01 00:00:00
abstract:INTRODUCTION:Psoriasis susceptibility locus 4 (PSORS4) is a susceptibility locus for psoriasis vulgaris (PsV), a common inflammatory, hyperproliferative skin disorder. Recently, a deletion of 2 late cornified envelope (LCE) genes within epidermal differentiation complex on chromosome 1 was shown to be enriched in 1426 ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.108951
更新日期:2010-05-01 00:00:00
abstract:OBJECTIVES:To show whether intra-articular steroid injections are effective in osteoarthritis; to determine factors that predict response; and to determine whether injection has a beneficial effect on muscle strength. METHODS:Double blind, placebo controlled, crossover study in 59 patients with symptomatic osteoarthri...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.55.11.829
更新日期:1996-11-01 00:00:00
abstract:OBJECTIVES:Systemic sclerosis (SSc) is a rare disease requiring multicentre collaboration to reveal comprehensive details of disease-related causes for morbidity and mortality. METHODS:The European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) group initiated a database to prospectively ga...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/annrheumdis-2011-200742
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVES:To determine whether hormonal dysfunction involving the hypothalamic-pituitary-adrenal (HPA) axis, prolactin (PRL) secretion, and sex hormone status contribute to development of systemic lupus erythematosus (SLE). METHODS:11 patients with SLE and 9 healthy controls were tested for their total anterior pitui...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.018325
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVE:To better understand the characteristics of synoviocytes located in the rheumatoid arthritis (RA) pannus. METHODS:One cell line, termed PSC, was cloned from RA pannus lesions. Phenotypic analysis was done by contrast microscopy, indirect immunostaining, and safranin O staining. Transcription of several proto...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.56.4.262
更新日期:1997-04-01 00:00:00
abstract:OBJECTIVES:To forecast, on the basis of the past and present position of rheumatologists in Europe, the competence needed in the future to secure and promote the specialty within the healthcare network. METHODS:Union Européenne des Médecins Spécialistes/European Board of Rheumatology (UEMS/EBR) questionnaire on (a) tr...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.59.8.580
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:The effect of adalimumab on hand osteoporosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for. METHODS:768 patients (537 fulfilled...
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/ard.2008.091264
更新日期:2009-07-01 00:00:00
abstract::The prevalence of anticardiolipin antibodies was evaluated in 70 children with juvenile chronic arthritis (JCA), in 25 adult patients with rheumatoid arthritis, in 42 healthy children and in 40 adult controls. Thirty seven (53%) patients with JCA were positive for IgG or IgM anticardiolipin antibodies, or both, and 30...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.50.9.599
更新日期:1991-09-01 00:00:00
abstract:OBJECTIVES:To review case histories of patients in whom fibrosis played a significant role in the pathogenesis of their disease, and to determine whether intravenous gammaglobulin (IVIg) contributed to the regression of their fibrotic condition. METHODS:Eight patients with excess fibrotic reaction in the course of div...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.62.2.175
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:Patients with rheumatoid arthritis (RA) have an increased risk of certain solid cancers, in particular lung cancer, compared to the general population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may further enhance this risk. OBJECTIVES:To compare the risk of solid cancer in patients with...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204851
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND:Recently, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration developed new classification criteria for rheumatoid arthritis (RA). OBJECTIVE:To evaluate the diagnostic and discriminative ability of these new criteria compared with the 1987 ACR criteria and the ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.148619
更新日期:2011-08-01 00:00:00
abstract::A novel, constitutively expressed and secreted interleukin 18 (IL18) binding protein (IL18BP) neutralises IL18. IL18BP shares many characteristics with soluble cytokine receptors of the IL1 family in that the protein exhibits specificity for IL18, belongs to the immunoglobulin-like class of receptors and has limited a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.59.suppl_1.i17
更新日期:2000-11-01 00:00:00
abstract:OBJECTIVE:To investigate the contributions towards hyperuricaemia of known risk factors, focusing on fractional (renal) clearance of urate (FCU) and variation in the ATP-binding cassette transporter, sub-family G 2 (ABCG2) gene. METHODS:The contributions of age, sex, ancestry, Q141K genotype for ABCG2, FCU, sugar-swee...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-208111
更新日期:2016-07-01 00:00:00
abstract:OBJECTIVE:To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS). PATIENTS AND METHODS:We include 1045 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological chara...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206418
更新日期:2016-02-01 00:00:00
abstract::Current drug development programs produce high quality data on the efficacy of new drugs, substantial data on safety, but little data on actual applicability of the new product compared to standard of care. After successful registration and launch, such data require years to accumulate and often remain incomplete. Thi...
journal_title:Annals of the rheumatic diseases
pub_type: 评论,杂志文章
doi:10.1136/ard.2009.110007
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVES:Previous evidence suggests the role of psychological stress in triggering the onset of autoimmunity. We aimed to investigate whether stress following major and minor life events could precede the onset of primary Sjögren's syndrome (pSS). The role of coping strategies and social support, as compensating buff...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.084152
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVE:To investigate the possibility of drug-free remission in patients with psoriatic arthritis (PsA) in continuous remission. METHODS:Prospective observational study in disease-modifying antirheumatic drug (DMARD)-treated PsA patients in continuous disease remission (no musculoskeletal symptoms, no or minimal sk...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204229
更新日期:2015-04-01 00:00:00
abstract:OBJECTIVE:To evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care. METHODS:Patients with SLE (185) with moderat...
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-2019-216379
更新日期:2020-03-01 00:00:00
abstract::The effect of immune complexes (IC) isolated from systemic lupus erythematosus (SLE) sera with polyethylene glycol and gel filtration on the chemotaxis and Fc receptor function of healthy monocytes was examined. Even at a low protein concentration (1 microgram/ml = 1 mg/l) ICs inhibit monocyte chemotaxis. ICs from pat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.5.729
更新日期:1984-10-01 00:00:00
abstract:BACKGROUND:The pathogenesis of the early stages of hand osteoarthritis is poorly understood, but recent high-resolution magnetic resonance imaging (hrMRI) studies suggest that the joint ligaments have a major role in the phenotypic expression of the disease. OBJECTIVE:To combine hrMRI and cadaveric histological studie...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.050112
更新日期:2006-10-01 00:00:00
abstract:OBJECTIVE:To investigate the rate of incident diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) and the impact of disease-modifying antirheumatic drug (DMARD) and statin treatments. METHODS:We studied patients with RA and ≥1 year participation in the National Data Bank for Rheumatic Diseases without ba...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2016-209954
更新日期:2017-05-01 00:00:00
abstract:OBJECTIVE:To evaluate radiographic features of osteoarthritis (OA) to determine which is more closely associated with knee pain and hence might be used as a radiographic definition of OA in the community. To evaluate joint space width in normal subjects. METHODS:452 subjects from a case-control community study of knee...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.57.10.595
更新日期:1998-10-01 00:00:00
abstract:OBJECTIVE:To study the feasibility and validity of a two-step telephone screening procedure for symptomatic knee and hip osteoarthritis (OA) in the general population. METHOD:The screening questionnaire was based on signs and symptoms, previous diagnosis of OA and validated OA criteria. A random sample of telephone nu...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.075952
更新日期:2008-10-01 00:00:00
abstract::It is postulated that the mobile inflamed joint may be subject to cyclical ischaemic reperfusion injury. Xanthine oxidoreductase is an enzyme thought to contribute to oxidative reperfusion injury, and the detection of this activity in human synovium is described. Three normal and five rheumatoid tissues were assayed w...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.46.11.843
更新日期:1987-11-01 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:BACKGROUND:There is emerging evidence that the development and progression of osteoarthritis (OA) is associated with inflammation. C reactive protein (CRP), a systemic marker for inflammation, may be elevated in OA patients but the evidence is conflicting. OBJECTIVE:To systematically review the literature for the rela...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1136/annrheumdis-2013-204494
更新日期:2015-04-01 00:00:00
abstract::One hundred consecutive admissions to an acute geriatric unit were examined for clinical and radiographic evidence of osteoarthritis (OA) and articular chondrocalcinosis (ACC). Thirty-four patients had ACC. This was age related, the prevalence rising from 15% in patients aged 65-74 years to 44% in patients over 84 yea...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.42.3.280
更新日期:1983-06-01 00:00:00