Abstract:
BACKGROUND:Nearly all secreted proteins are glycosylated, and serum glycoproteins that exhibit disease-associated glycosylation changes have potential to be biomarkers. In rheumatoid arthritis (RA), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) are widely used as serologic biomarkers, but they lack sufficient specificity or precision. We performed comparative glycosylation profiling of MMP-3 using a recently developed antibody-overlay lectin microarray technology that allows semicomprehensive and quantitative analysis of specific protein glycosylation to develop an RA-specific disease activity biomarker. METHODS:Serum was taken from patients with RA (n = 24) whose disease activity was scored using composite measures, and MMP-3 was immunoprecipitated and subjected to lectin microarray analysis. A disease activity index (DAI) based on lectin signal was developed and validated using another cohort (n = 60). Synovial fluid MMP-3 in patients with RA and patients with osteoarthritis (OA) was also analyzed. RESULTS:Intense signals were observed on a sialic acid-binding lectin (Agrocybe cylindracea galectin [ACG]) and O-glycan-binding lectins (Jacalin, Agaricus bisporus agglutinin [ABA], and Amaranthus caudatus agglutinin [ACA]) by applying subnanogram levels of serum MMP-3. ACG, ABA, and ACA revealed differences in MMP-3 quantity, and Jacalin revealed differences in MMP-3 quality. The resultant index, ACG/Jacalin, correlated well with disease activity. Further validation using another cohort confirmed that this index correlated well with several DAIs and their components, and reflected DAI changes following RA treatment, with correlations greater than those for MMP-3 and CRP. Furthermore, MMP-3, which generated a high ACG/Jacalin score, accumulated in synovial fluid of patients with RA but not in that of patients with OA. Sialidase digestion revealed that the difference in quality was derived from O-glycan α-2,6-sialylation. CONCLUSIONS:This is the first report of a glycoprotein biomarker using glycan change at a local lesion to assess disease activity in autoimmune diseases. Differences in the degree of serum MMP-3 α-2,6-sialylation may be a useful index for estimating disease activity.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Takeshita M,Kuno A,Suzuki K,Matsuda A,Shimazaki H,Nakagawa T,Otomo Y,Kabe Y,Suematsu M,Narimatsu H,Takeuchi Tdoi
10.1186/s13075-016-1013-2subject
Has Abstractpub_date
2016-05-21 00:00:00pages
112issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-016-1013-2journal_volume
18pub_type
杂志文章abstract:INTRODUCTION:Interferon alpha (IFN-α) has a complex role in autoimmunity, in that it may both enhance and prevent inflammation. We have previously shown that the presence of IFN-α at sensitization protects against subsequent antigen-triggered arthritis. To understand this tolerogenic mechanism, we performed a descripti...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4326
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abstract::The discovery of the receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) system and its role in the regulation of bone resorption exemplifies how both serendipity and a logic-based approach can identify factors that regulate cell function. Before this discovery in the mid to late 1990...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2165
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s13075-015-0728-9
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abstract::Ankylosing spondylitis (AS) is a member of the family of spondyloarthropathies, which are inflammatory arthritides largely involving the axial skeleton and commonly accompanied by peripheral arthritis. Genetic factors, particularly the presence of HLA-B27, are major contributors to the susceptibility for AS. Despite s...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1012
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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
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更新日期:2012-04-02 00:00:00
abstract:: ...
journal_title:Arthritis research & therapy
pub_type: 信件
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abstract::The accumulation of T cells in the synovial membrane is the crucial step in the pathophysiology of the inflammatory processes characterizing juvenile idiopathic arthritis (JIA). In this study, we evaluated the expression and the pathogenetic role in oligoarticular JIA of a CXC chemokine involved in the directional mig...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3050
更新日期:2010-01-01 00:00:00
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journal_title:Arthritis research & therapy
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更新日期:2018-05-02 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4157
更新日期:2013-01-29 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar790
更新日期:2003-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1155
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/ar4442
更新日期:2014-01-17 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 评论,社论
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更新日期:2014-07-30 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2008-01-01 00:00:00
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2015-08-28 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2018-06-07 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,已发布勘误
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更新日期:2018-11-05 00:00:00
abstract:INTRODUCTION:Despite growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was to detect the levels of ...
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更新日期:2015-05-21 00:00:00
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journal_title:Arthritis research & therapy
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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,meta分析,评审
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更新日期:2015-12-15 00:00:00
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pub_type: 杂志文章
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更新日期:2020-09-20 00:00:00