Abstract:
OBJECTIVES:There is a need to identify effective treatments for rheumatic diseases, and while genetic studies have been successful it is unclear which genes contribute to the disease. Using our existing Capture Hi-C data on three rheumatic diseases, we can identify potential causal genes which are targets for existing drugs and could be repositioned for use in rheumatic diseases. METHODS:High confidence candidate causal genes were identified using Capture Hi-C data from B cells and T cells. These genes were used to interrogate drug target information from DrugBank to identify existing treatments, which could be repositioned to treat these diseases. The approach was refined using Ingenuity Pathway Analysis to identify enriched pathways and therefore further treatments relevant to the disease. RESULTS:Overall, 454 high confidence genes were identified. Of these, 48 were drug targets (108 drugs) and 11 were existing therapies used in the treatment of rheumatic diseases. After pathway analysis refinement, 50 genes remained, 13 of which were drug targets (33 drugs). However considering targets across all enriched pathways, a further 367 drugs were identified for potential repositioning. CONCLUSION:Capture Hi-C has the potential to identify therapies which could be repositioned to treat rheumatic diseases. This was particularly successful for rheumatoid arthritis, where six effective, biologic treatments were identified. This approach may therefore yield new ways to treat patients, enhancing their quality of life and reducing the economic impact on healthcare providers. As additional cell types and other epigenomic data sets are generated, this prospect will improve further.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Martin P,Ding J,Duffus K,Gaddi VP,McGovern A,Ray-Jones H,Yarwood A,Worthington J,Barton A,Orozco Gdoi
10.1136/annrheumdis-2018-214649subject
Has Abstractpub_date
2019-08-01 00:00:00pages
1127-1134issue
8eissn
0003-4967issn
1468-2060pii
annrheumdis-2018-214649journal_volume
78pub_type
杂志文章abstract:BACKGROUND:An imbalance in cytokine homoeostasis is thought to have a key role in the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), and recently, a role for chemokines has been noted. OBJECTIVE:To compare concentrations of monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebral spinal fluid (CSF)...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.041640
更新日期:2006-02-01 00:00:00
abstract::Feverfew, reputed by folklore to be effective in arthritis, has in vitro properties that could be beneficial in the control of inflammatory disease. Forty one female patients with symptomatic rheumatoid arthritis received either dried chopped feverfew (70-86 mg) or placebo capsules once daily for six weeks. Allocation...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/ard.48.7.547
更新日期:1989-07-01 00:00:00
abstract::Twenty-five patients (22 males and 3 females) are described who had 'unclassifiable' seronegative peripheral arthritis affecting mainly the large joints of the lower limbs with other typical features of spondyloarthropathies such as heel pain, low back pain, and mucosal ulcers. But their disorders could not be diagnos...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.42.6.640
更新日期:1983-12-01 00:00:00
abstract:OBJECTIVE:To determine if serum urate concentration is associated with development of hypertension in young adults. METHODS:Retrospective cohort analysis from 4752 participants with available serum urate and without hypertension at baseline from the Coronary Artery Risk Development in Young Adults (CARDIA) study; a mi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-201916
更新日期:2013-08-01 00:00:00
abstract:OBJECTIVES:Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200657
更新日期:2012-09-01 00:00:00
abstract:OBJECTIVES:Autophagy has recently been shown to regulate osteoclast activity and osteoclast differentiation. Here, we aim to investigate the impact of autophagy inhibition as a potential therapeutic approach for the treatment of osteoporosis in preclinical models. METHODS:Systemic bone loss was induced in mice by gluc...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-207240
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:PATIENTS with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions. OBJECTIVES:To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide. METHODS: STUDY DESIGN:international, cross-sectional. PATIENTS:consecutiv...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204223
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:There is increased cardiovascular disease mortality in rheumatoid arthritis. This may reflect an increased prevalence of cardiovascular disease or an increased case fatality in patients with rheumatoid arthritis. OBJECTIVES:To examine whether rheumatoid patients with disease onset in the 1980s-1990s have in...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2004.034777
更新日期:2005-11-01 00:00:00
abstract:OBJECTIVE:To characterise activation of the type I interferon (IFN) pathway in patients with systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), rheumatoid arthritis (RA) and systemic scleroderma (SSc) and to evaluate the potential to develop a molecular diagnostic tool from the peripheral bloo...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2011.150326
更新日期:2011-11-01 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:OBJECTIVE:To determine the clinical features associated with histologically proven rheumatoid vasculitis (HRV) and the additional diagnostic value of serological markers in an inception cohort of 81 patients with rheumatoid arthritis (RA) suspected of RV. METHODS:The presence and number of recently developed extra-art...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.62.5.407
更新日期:2003-05-01 00:00:00
abstract:OBJECTIVE:To compare the efficacy and safety between tocilizumab added to methotrexate and tocilizumab switched from methotrexate in patients with active rheumatoid arthritis (RA). METHODS:This is a 2-year randomised, controlled study. RA patients with moderate or high disease activity despite methotrexate were random...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2015-208426
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVES:Classification criteria are biased towards classifying long-standing disease. We compared the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)-2019, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and ACR-1997 criteria in an early (median 48 months) systemic l...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2019-216155
更新日期:2020-02-01 00:00:00
abstract:OBJECTIVE:To assess sensory function in skin overlying the joints of patients with rheumatoid arthritis, in relation to the pain and tenderness which commonly arises in structures not directly involved in the inflammatory process. METHODS:An intradermal injection of capsaicin 0.05 microgram in 10 microliters was made ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.4.251
更新日期:1995-04-01 00:00:00
abstract::A simple method is described which allows sequential monitoring of the endocytic activity of blood and synovial fluid cells from rheumatoid arthritis patients undergoing therapy with levamisole. Evidence of immediate (24 hours) and long-term (5-7 weeks) cellular phagocytic enhancement is presented. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.40.4.382
更新日期:1981-08-01 00:00:00
abstract:OBJECTIVES:To develop a preliminary composite psoriatic disease activity index (CPDAI) for psoriasis and psoriatic arthritis. METHODS:Five domains were assessed and specific instruments were employed for each domain to determine the extent of domain involvement and the effect of that involvement on quality of life/fun...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2010.129379
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:Collagen-induced arthritis (CIA) is the most commonly used model of rheumatoid arthritis (RA). In both CIA and RA there is an increase in the cellular content of the synovium, this being dominated by macrophages. OBJECTIVE:To assess the impact of etoposide, a topoisomerase II antagonist known to induce mono...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.9.829
更新日期:2002-09-01 00:00:00
abstract:OBJECTIVES:To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy. METHODS:Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an int...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1136/annrheumdis-2011-200941
更新日期:2012-11-01 00:00:00
abstract:OBJECTIVE:To determine the frequency and suppressive capacity of regulatory T cells (T(reg)) and their association with clinical parameters in patients with systemic scleroderma (SSc). METHODS:Peripheral blood from 25 patients with SSc, 15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.116525
更新日期:2011-08-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.10.682
更新日期:1985-10-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2020-218902
更新日期:2020-11-04 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2016-209958
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVES:To evaluate the risk of septic arthritis (SA) in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. METHODS:Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, the authors compared the risk of SA between 11 ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2011.152769
更新日期:2011-10-01 00:00:00
abstract::Antibodies to cytomegalovirus (CMV) and Epstein-Barr virus capsid antigen (EBVCA) were examined in 41 patients with rheumatoid arthritis (RA), 26 patients with primary sicca syndrome, and 26 healthy subjects of similar age and sex. IgG antibody titres to EBVCA and CMV were similar in all three groups, apart from a tri...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.11.742
更新日期:1985-11-01 00:00:00
abstract::The question 'Does the use of second-line therapy confer long-term benefit on outcome measures in rheumatoid arthritis?' remains unanswered. The major obstacle which prevents collection of the necessary data is the lack of a suitable control group. In this report experience with three 'second-line placebo groups' is d...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,评审
doi:10.1136/ard.44.2.134
更新日期:1985-02-01 00:00:00
abstract:OBJECTIVE:To identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations. METHODS:High-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 heal...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200661
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:The Health Assessment Questionnaire Disability Index (HAQ-DI) is the most widely used measure of function in rheumatoid arthritis (RA). OBJECTIVE:To evaluate individualised forms of the HAQ-DI and thus enhance the incorporation of patients' views in outcome assessment. PATIENTS AND METHODS:HAQ-DI data were...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.102137
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVES:To evaluate the effect of infliximab on health related quality of life (HRQoL) and physical function in patients with active psoriatic arthritis (PsA) in the IMPACT 2 trial. METHODS:200 patients with PsA unresponsive to conventional treatment were randomised to intravenous infusions of infliximab 5 mg/kg or...
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.2005.040196
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:To further explore deiodinase iodothyronine type 2 (DIO2) as a therapeutic target in osteoarthritis (OA) by studying the effects of forced mechanical loading on in vivo joint cartilage tissue homeostasis and the modulating effect herein of Dio2 deficiency. METHODS:Wild-type and C57BL/6-Dio2(-/-) -mice were s...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206608
更新日期:2016-03-01 00:00:00
abstract:OBJECTIVES:To study the pathogenesis of pneumomediastinum in polymyositis/dermatomyositis (PM/DM). PATIENTS AND METHODS:The clinical records of 48 patients with PM/DM were reviewed, focusing mainly on the presence of pneumomediastinum and cutaneous vasculopathy, and the chest radiographic changes. A patient with pneum...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.59.5.372
更新日期:2000-05-01 00:00:00