Abstract:
BACKGROUND:The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relationship between autoantibody targets has not been systematically explored. Protein-protein interaction and pathway analyses were conducted to identify pathways relevant to disease, using autoantibody targets and gene products of IIM-associated single nucleotide polymorphism (SNP) loci. METHODS:Protein-protein interactions were analysed using Disease Association Protein-Protein Link Evaluator (DAPPLE). Gene ontology and pathway analyses were conducted using Database for Annotation Visualisation and Integrated Discovery (DAVID) and Gene Relationships Across Implicated Loci (GRAIL). Analyses were undertaken including the targets of published autoantibodies, significant and suggestive SNPs from an IIM association study and autoantibody targets plus SNPs combined. RESULTS:The protein-protein interaction networks formed by autoantibody targets and associated SNPs showed significant direct and/or indirect connectivity (p < 0.05). Autoantibody targets plus associated SNPs combined resulted in more significant indirect and common interactor connectivity, suggesting autoantibody targets and proteins encoded by IIM-associated loci may be involved in common pathways. Tumour necrosis factor receptor-associated factor 6 (TRAF6) was identified as a hub protein, and UBE3B, HSPA1A, HSPA1B and PSMD3 also were identified as genes with significant connectivity. Pathway analysis identified that autoantibody targets and associated SNP regions are significantly interconnected (p < 0.01), and confirmed autoantibody target involvement in translational and post-translational processes. 'Ubiquitin' was the only keyword strongly linking significant genes across regions in all three GRAIL analyses of autoantibody targets and IIM-associated SNPs. CONCLUSIONS:Autoantibody targets and IIM-associated loci show significant connectivity and inter-relatedness, and identify several key genes and pathways in IIM pathogenesis, possibly mediated via the ubiquitination pathway.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Parkes JE,Rothwell S,Day PJ,McHugh NJ,Betteridge ZE,Cooper RG,Ollier WE,Chinoy H,Lamb JA,Myositis Genetics Consortium (MYOGEN).doi
10.1186/s13075-016-1061-7subject
Has Abstractpub_date
2016-07-07 00:00:00pages
156issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-016-1061-7journal_volume
18pub_type
杂志文章abstract::Treatment of Sjögren's syndrome is almost entirely symptomatic. A lack of true understanding of the underlying immunological pathology of the disease prevents directed therapy. Interleukin-21 (IL-21) is elevated in the serum of patients with this disease and is expressed by the lymphocytes infiltrating the salivary gl...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3518
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Adjustment of infliximab dosage for individuals may be useful in improving therapeutic response in rheumatoid arthritis (RA). Herein, we aimed to determine whether measurement of infliximab serum concentration modifies the therapeutic decision and improves the control of disease activity. METHODS:RA patie...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar2867
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a p...
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/ar2740
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abstract::Scleroderma (systemic sclerosis; SSc) is characterised by fibrosis of the skin and internal organs in the context of autoimmunity and vascular perturbation. Overproduction of extracellular matrix components and loss of specialised epithelial structures are analogous to the process of scar formation after tissue injury...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4230
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2844
更新日期:2009-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2780
更新日期:2009-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2198
更新日期:2007-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2817
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3830
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abstract::Lupus nephritis is a major contributor to morbidity and mortality in systemic lupus erythematosus, but little is known about the pathogenic processes that underlie the progressive decay in renal function. A common finding in lupus nephritis is thickening of glomerular basement membranes associated with immune complex ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2532
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is a rare disease with studies limited by small sample sizes. Electronic health records (EHRs) represent a powerful tool to study patients with rare diseases such as SSc, but validated methods are needed. We developed and validated EHR-based algorithms that incorporate billing codes ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2092-7
更新日期:2019-12-30 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3108
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:The SPARCC sacroiliac joint inflammation (SIS) and structural (SSS) scores are reliable measures to quantify abnormalities in the pediatric sacroiliac joint. We aimed to evaluate the utility of online calibration modules for the SIS and SSS and the reliability of their component change scores. METHODS:Chang...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02157-4
更新日期:2020-03-24 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2019
更新日期:2006-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2581
更新日期:2008-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3689
更新日期:2012-01-18 00:00:00
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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
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3758
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3481
更新日期:2011-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar3064
更新日期:2010-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3827
更新日期:2012-05-01 00:00:00
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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
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4368
更新日期:2013-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-2122-5
更新日期:2020-03-04 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4179
更新日期:2013-02-20 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4067
更新日期:2012-10-19 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1458
更新日期:2005-01-01 00:00:00
abstract::Systemic lupus erythematosus is a prototypic autoimmune disease characterized by autoantibody production and immune complex formation/deposition in target organs such as the kidney. Resultant local inflammation then leads to organ damage. Nephritis, a major cause of morbidity and mortality in patients with lupus, occu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/ar3500
更新日期:2011-01-01 00:00:00