Correction to: Proteomic analysis of human synovial fluid reveals potential diagnostic biomarkers for ankylosing spondylitis.
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SUBMITTER: Lee JH
PROVIDER: S-EPMC10474741 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Correction to: Proteomic analysis of human synovial fluid reveals potential diagnostic biomarkers for ankylosing spondylitis.
Lee Ji-Hyun JH Jung Jae Hun JH Kim Jeesoo J Baek Won-Ki WK Rhee Jinseol J Kim Tae-Hwan TH Kim Sang-Hyon SH Kim Kwang Pyo KP Son Chang-Nam CN Kim Jong-Seo JS
Clinical proteomics 20230902 1
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Project description:BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. The etiology of this disease remains poorly understood, but interactions between genetic and environmental factors have been implicated. The present study identified differentially expressed proteins in the synovial fluid (SF) of AS patients to elucidate the underlying cause of AS.MethodsA cohort of 40 SF samples from 10 AS and 10 each of rheumatoid arthritis (RA), gout, and osteoarthritis (OA) patients were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins specific to AS. The label-free LC-MS/MS results were verified by western blotting.ResultsWe identified 8 proteins that were > 1.5-fold upregulated in the SF of AS patients compared to that of the disease control groups, including HP, MMP1, MMP3, serum amyloid P-component (APCS), complement factor H-related protein 5 (CFHR5), mannose-binding lectin 2 (MBL2), complement component C9 (C9), and complement C4-A (C4A). CFHR5 and C9 were previously found in serum from AS patients, while APCS was previously found in SF as well as in serum. However, the present study has identified C4A, and MBL2 as potential AS biomarkers for the first time. The expression levels of MMP3, C9, and CFHR5 were verified in AS SF using western blotting.ConclusionWe performed quantitative comparative proteomic analysis using by LC-MS/MS of the SF from four disease states: RA, gout, and OA. This systematic comparison revealed novel differentially expressed proteins in AS SF, as well as two previously reported candidate biomarkers. We further verified the expression of MMP3, C9 and CFHR5 by western blot. These proteins may serve as diagnostic or prognostic biomarkers in patients with AS, and may thus improve the clinical outcomes of this serious disease.
| S-EPMC7269004 | biostudies-literature
Project description:[Background] Ankylosing spondylitis (AS), affecting 0.5% of the population, is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. The etiology of this disease is still poorly understood, but it may be involved with the interaction of genetic and environmental factors. Our aim was to identify differentially expressed protein mediators in synovial fluid (SF) of AS. [Methods] A Total of 40 SF samples from 10 AS and each 10 controls [Osteoarthritis (OA), Rheumatoid Arthritis (RA), gouty arthritis (Gout)] were collected. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) were used to identify differentially expressed proteins based on the label free quantification (MaxLFQ). Among the 9 proteins with fold changes of > 1.5, the 8 proteins were verified with the exception of the abundant protein Haptoglobin (HP). Matrix metalloproteinase-1(MMP1) and Matrix metalloproteinase-3(MMP3) were used as a positive control, and the remaining 6 proteins were subjected to western blot analysis. [Results] We identified 9 proteins that were found to be more than 1.5-fold differentially expressed in SF of AS patients compared to control groups. Proteins such as HP, MMP1, MMP3, Serum amyloid P-component(APCS), Complement factor H-related protein 5(CFHR5), Fumarylacetoacetase(FAH), Mannose-binding lectin 2(MBL2), Complement component C9(C9) and Complement C4-A(C4A) were found to be upregulated in the SF of AS patients. CFHR5 and C9 were reported in previous studies with AS serum. APCS was reported in SF as well as serum. However, FAH, C4A and MBL2 were newly discovered through this analysis. We were able to verify the unique expression level of C9 and CFHR5 in AS sample using western blot analysis compared to the other three diseases. [Conclusions] We performed quantitative proteomic analysis of the respective SF sample from 4 diseases,i.e., AS, OA, RA, and GOUT, by LC-MS/MS. The systematic comparative proteomic analysis of the four groups together was carried out for the first time, leading to several differentially expressed proteins in AS. Among them, we expect C9 and CFHR5, which expression level were confirmed by western blot analysis and will be further validated by ELISA, can be a potential biomarkers for AS.
2021-07-15 | PXD016620 | Pride
Project description:BackgroundWe sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity.MethodsWe studied biologic-treatment-naïve AS and healthy control (HC) patients' sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters in protein-protein interaction networks and Ingenuity Pathway Analysis (IPA) for upstream regulators. Lasso regression analysis was performed for diagnosis.ResultsOf the 1317 proteins detected in our diagnosis and monitoring analyses, 367 and 167 (317 and 59, FDR-corrected q < .05) DEPs, respectively, were detected. MCODE identified complement, IL-10 signaling, and immune/interleukin signaling as the top 3 diagnosis PPI clusters. Complement, extracellular matrix organization/proteoglycans, and MAPK/RAS signaling were the top 3 monitoring PPI clusters. IPA showed interleukin 23/17 (interleukin 22, interleukin 23A), TNF (TNF receptor-associated factor 3), cGAS-STING (cyclic GMP-AMP synthase, Stimulator of Interferon Gene 1), and Jak/Stat (Signal transducer and activator of transcription 1), signaling in predicted upstream regulators. Lasso regression identified a Diagnostic 13-protein model predictive of AS. This model had a sensitivity of 0.75, specificity of 0.90, a kappa of 0.59, and overall accuracy of 0.80 (95% CI: 0.61-0.92). The AS vs HC ROC curve was 0.79 (95% CI: 0.61-0.96).ConclusionWe identified multiple candidate AS diagnostic and disease activity monitoring serum biomarkers using a comprehensive proteomic screen. Enrichment analysis identified key pathways in AS diagnosis and monitoring. Lasso regression identified a multi-protein panel with modest predictive ability.
| S-EPMC10088143 | biostudies-literature
Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.
2012-12-01 | E-GEOD-41038 | biostudies-arrayexpress
Project description:Single-cell transcriptome of >55,000 cells multiplexed into 4 channels obtained from peripheral blood and synovial fluid of two patients with HLA-B27+ ankylosing spondylitis,.
2021-10-18 | E-MTAB-10948 | biostudies-arrayexpress
Project description:Exosomes extracted from synovial fluid (SF-exo) reflect the status of their originating cells. The proteomic profiles of SF-exo are important for the diagnosis of osteoarthritis (OA). To delineate the proteomic differences between SF-exo from OA patients and healthy individuals, a quantitative proteomic study based on iTRAQ technology was performed. In this study, a total of 439 proteins were identified, with 20 proteins exhibiting increased expression in the OA patient group, while 5 showed decreased expression levels. Bioinformatic analysis showed these differentially expressed proteins (DEPs) were involved in a variety of immune-related processes, including complement activation and antigen binding. For further screening, we downloaded a publicly available dataset of synovial fluid (PXD023708) and compared it with our dataset. The comparative Results identified that 5 DEPs overlapped in two datasets, and protein-protein interaction revealed that C3, C4B and APOM were key members of a tightly interactive network. Through receiver operating characteristic (ROC) curve analysis and enzyme-linked immunosorbent assay (ELISA), we confirmed 5 DEPs (C3, C4B, APOM, MMP3, DPYSL2) as potential diagnostic biomarkers for OA. And Pearson correlation analysis confirmed that most of these biomarkers had no significant linear correlation with age. Overall, our study provides the first comprehensive description of the proteomic landscape of SF-exo in OA and identifies several potential biomarkers. These findings are expected to provide valuable insights into the diagnosis and treatment of OA.
| S-EPMC11658229 | biostudies-literature
Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling.
2012-12-01 | GSE41038 | GEO
Project description:BackgroundThe assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease.ResultsTo investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentially abundant between ankylosing spondylitis patients and healthy controls. Patients were characterized by a form of gut microbial dysbiosis that is more prominent than previously reported cases with inflammatory bowel disease. Specifically, the ankylosing spondylitis patients demonstrated increases in the abundance of Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus, which is commonly used in probiotics, accumulated in the ankylosing spondylitis patients. Diagnostic algorithms were established using a subset of these gut microbial biomarkers.ConclusionsAlterations of the gut microbiome are associated with development of ankylosing spondylitis. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.
| S-EPMC5530561 | biostudies-literature
Project description:Whole blood RNA-sequencing data from 5 AS patients who met 1984 AS criteria and 3 healthy human were obtained to gain insight into the potential mechanism of ankylosing spondylitis.
2021-11-10 | GSE181364 | GEO
Project description:Objective. Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton. Early and accurate diagnosis is necessary for the timely and effective treatment of this disease and its common complications. Lipid metabolites form various kinds of bioactive molecules that regulate the initiation and progression of inflammation. However, there are currently few studies that investigate the alteration of serum lipid in AS patients. Methods. Blood samples were collected from 115 AS patients and 108 healthy controls (HCs). Serum-untargeted lipidomics were performed using ultrahigh-performance liquid chromatography coupled with Q-Exactive spectrometry, and the data were determined by multivariate statistical methods to explore potential lipid biomarkers. Results. Lipid phenotypes associated with disease activity were detected in the serum of patients with AS. Of all 586 identified lipids, there are 297 differential lipid metabolites between the AS and HC groups, of which 15 lipid metabolites are significant. In the AS groups, the levels of triacylglycerol (TAG) (18:0/18:1/20:0) were increased, and the levels of phosphatidylcholine (PC) (16:0e/26:4) and PC (18:1/22:6) were decreased. The areas under the receiver operating characteristic curve (AUC) of TAG (18:0/18:1/20:0), PC (16:0e/26:4), and PC (18:1/22:6) were 0.919, 0.843, and 0.907, respectively. Conclusion. Our findings uncovered that lipid deregulation is a crucial hallmark of AS, thereby providing new insights into the early diagnosis of AS.
| S-EPMC9855684 | biostudies-literature