Transcriptome analysis of ankylosing spondylitis patients before and after TNF-α inhibitor therapy reveals the pathways affected
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE141646 | GEO | 2019/12/10
REPOSITORIES: GEO
Similar Datasets
Project description:Ankylosing spondylitis (AS) is a type of spondyloarthropathies, the diagnosis of which is often delayed. The lack of early diagnosis tools often delays the institution of appropriate therapy. This study aimed to investigate the systemic metabolic shifts associated with AS and TNF inhibitors treatment. Additionally, we aimed to define reliable serum biomarkers for the diagnosis. We employed an untargeted technique, ultra-performance liquid chromatography-mass spectroscopy (LC-MS), to analyze the serum metabolome of 32 AS individuals before and after 24-week TNF inhibitors treatment, as well as 40 health controls (HCs). Multivariate and univariate statistical analyses were used to profile the differential metabolites associated with AS and TNF inhibitors. A diagnostic panel was established with the least absolute shrinkage and selection operator (LASSO). The pathway analysis was also conducted. A total of 55 significantly differential metabolites were detected. We generated a diagnostic panel comprising five metabolites (L-glutamate, arachidonic acid, L-phenylalanine, PC (18:1(9Z)/18:1(9Z)), 1-palmitoylglycerol), capable of distinguishing HCs from AS with a high AUC of 0.998, (95%CI: 0.992-1.000). TNF inhibitors treatment could restore the equilibrium of 21 metabolites. The most involved pathways in AS were amino acid biosynthesis, glycolysis, glutaminolysis, fatty acids biosynthesis and choline metabolism. This study characterized the serum metabolomics signatures of AS and TNF inhibitor therapy. We developed a five-metabolites-based panel serving as a diagnostic tool to separate patients from HCs. This serum metabolomics study yielded new knowledge about the AS pathogenesis and the systemic effects of TNF inhibitors.
| S-EPMC7933516 | biostudies-literature
Project description:Transcriptome analysis of ankylosing spondylitis patients before and after TNF-α inhibitor therapy reveals the pathways affected
| PRJNA594302 | ENA
Project description:We aim to generate an artificial neural network (ANN) model to predict early TNF inhibitor users in patients with ankylosing spondylitis. The baseline demographic and laboratory data of patients who visited Samsung Medical Center rheumatology clinic from Dec. 2003 to Sep. 2018 were analyzed. Patients were divided into two groups: early-TNF and non-early-TNF users. Machine learning models were formulated to predict the early-TNF users using the baseline data. Feature importance analysis was performed to delineate significant baseline characteristics. The numbers of early-TNF and non-early-TNF users were 90 and 505, respectively. The performance of the ANN model, based on the area under curve (AUC) for a receiver operating characteristic curve (ROC) of 0.783, was superior to logistic regression, support vector machine, random forest, and XGBoost models (for an ROC curve of 0.719, 0.699, 0.761, and 0.713, respectively) in predicting early-TNF users. Feature importance analysis revealed CRP and ESR as the top significant baseline characteristics for predicting early-TNF users. Our model displayed superior performance in predicting early-TNF users compared with logistic regression and other machine learning models. Machine learning can be a vital tool in predicting treatment response in various rheumatologic diseases.
| S-EPMC7679386 | biostudies-literature
Project description:ObjectivesAnkylosing spondylitis (AS) is challenging to diagnose in its early stages, and treatment options are limited.MethodsGEO2R analysis and weighted gene co-expression network analysis (WGCNA) were used to identify DEGs and key modules. Kyoto Encyclopedia of Genes and Genomes analysis and Protein-protein interactions were used to identify core genes. Receiver operating characteristic curve, chi-square and t-test were used to analyze the correlation between gene expression and clinicopathological characteristics. Gene expression was detected using Real-time polymerase chain reaction and western blotting.ResultsGEO2R analysis and WGCNA identified 1100 DEGs and brown module. The KEGG analysis revealed that 444 core genes were closely associated with specific pathways. PPIs demonstrated that a key module, consisting of 6 genes, was linked to the phagosome pathway. NCF4, identified as an effective biomarker, was selected for diagnosing AS. Bioinformatics analyses indicated that NCF4 could be associated with important clinical markers. RT-PCR and western blotting showed increased expression of NCF4 in AS, which decreased after anti-TNF therapy.ConclusionsAnti-TNF therapy may exert its therapeutic function by inhibiting NCF4 expression, hence controlling the phagosome pathway. NCF4 has the potential to function as a diagnostic and prognostic biomarker for AS.
| S-EPMC10483821 | biostudies-literature
Project description:BackgroundTNF inhibiting drugs (TNFi) provide symptomatic relief for patients with ankylosing spondylitis (AS), but uncertainty remains about long-term benefits. We compared hospital admissions, emergency department (ED) presentations, and direct health care costs before and after the availability of subsidized TNFi therapy for AS patients.MethodsState-specific dispensing and cost data for TNFi therapy for AS in Western Australia (WA) were obtained from Pharmaceutical Benefits Scheme (PBS) and expressed as the number of defined daily doses (DDD)/1000 population/day. Linked admission and ED data for 1783 AS patients followed for 14,257 person-years between 1990 and 2015 were extracted. Pre- and post-2005 admission rates/100,000 population were compared by rate ratio (RR).ResultsTNFi uptake in WA reached a DDD/1000 population/day 0.45 at an annual cost of AU$17.7 million in 2020. Hospital admission rates remained unchanged (RR: 0.95, CI 0.71-1.27, p = 0.66) but increased slightly in female patients (RR 1.22; CI 0.91-1.64, p = 0.20). While there was no change in cardiovascular admissions (6.3 vs. 6.2%, p = 0.6) or ED visit rates since 2005, frequency for cancer (2.7 vs. 3.8%, p < 0.01), infection (1.1 vs. 1.7%, p < 0.01) and mental health (4.0 vs. 4.5%, p < 0.02) admissions increased. Associated direct health care costs (2020 values) averaged AU$14.7 million before and AU$ 24.7 million per year after 2005.ConclusionsThe introduction of subsidized TNFi therapy did not change all-cause hospital admission or ED visit rates for existing AS patients. Whether the significantly increased direct health care costs are offset by reductions in other health care costs remains to be determined.
| S-EPMC8814256 | biostudies-literature
Project description:The study identifies allograft inflammatory factor-1 (AIF-1) as a key marker of interferon (IFN) signature, which differentiates TNF inhibitor (TNFi) responders from non-responders in ankylosing spondylitis (AS)
2025-05-02 | GSE277791 | GEO
Project description:To identify molecular factor that can predicts TNF inhibitor responsiveness for Ankylosing spondylitis patients. We performed scRNA-seq and CITE-seq before and after TNF or IL17 inhibitor treatment.
2025-05-02 | GSE277117 | GEO
Project description:BackgroundClinical characteristics and manifestations of psoriatic arthritis (PsA) have been extensively studied in western countries, yet data of Korean patients with PsA are very limited. We aimed to investigate the clinical traits of patients with PsA and dissect the characteristics of those with axial involvement.MethodsIn this observational study, we analyzed clinical data of 109 patients with PsA who were enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry between December 2012 and March 2022 at the time point of initiating or switching to a biologic agent. Data from 2,221 patients with ankylosing spondylitis (AS) registered during the same period were also analyzed. We divided patients with PsA into patients with or without axial involvement and then added AS patients with psoriasis (total three subgroups) for comparative analyses.ResultsAsymmetric oligoarthritis was the most common clinical manifestation in patients with PsA, followed by symmetric polyarthritis and spondylitis. Our analysis indicated that methotrexate and sulfasalazine were the two most prescribed disease-modifying antirheumatic drugs for patients with PsA before starting biologic therapy. The patients with psoriatic spondylitis had more peripheral joint involvement (P = 0.016), less prior uveitis (P < 0.001), and lower human leukocyte antigen B27 (HLA-B27) positivity (P < 0.001) than the AS patients with psoriasis. Furthermore, syndesmophytes and radiographic sacroiliitis were prevalent among patients with PsA and AS patients with psoriasis who had the HLA-B27 gene.ConclusionOur study shows that the degree of peripheral arthritis is less severe in Korean patients with PsA who require biologics and reestablishes that psoriatic spondylitis is a common and important clinical pattern in Korean patients with PsA.Trial registrationClinicalTrials.gov Identifier: NCT01965132.
| S-EPMC9424747 | biostudies-literature
Project description:The etiology of Ankylosing spondylitis (AS) is still unknown and the identification of the involved molecular pathogenetic pathways is a current challenge in the study of the disease. Adalimumab (ADA), an anti-tumor necrosis factor (TNF)-alpha agent, is used in the treatment of AS. We aimed at identifying pathogenetic pathways modified by ADA in patients with a good response to the treatment. Gene expression analysis of Peripheral Blood Cells (PBC) from six responders and four not responder patients was performed before and after treatment. Differentially expressed genes (DEGs) were submitted to functional enrichment analysis and network analysis, followed by modules selection. Most of the DEGs were involved in signaling pathways and in immune response. We identified three modules that were mostly impacted by ADA therapy and included genes involved in mitogen activated protein (MAP) kinase, wingless related integration site (Wnt), fibroblast growth factor (FGF) receptor, and Toll-like receptor (TCR) signaling. A separate analysis showed that a higher percentage of DEGs was modified by ADA in responders (44%) compared to non-responders (12%). Moreover, only in the responder group, TNF, Wnt, TLRs and type I interferon signaling were corrected by the treatment. We hypothesize that these pathways are strongly associated to AS pathogenesis and that they might be considered as possible targets of new drugs in the treatment of AS.
| S-EPMC5406874 | biostudies-literature
Project description:The aim of this study was to seek more novel ankylosing spondylitis (AS)-associated DNA methylation. Genome wide DNA methylation profiling was profiled in peripheral blood mononuclear cells (PBMCs) from 24 individuals (AS: health controls (HCs) = 12:12) with high-throughput array. The Illumina Infinium MethylationEPIC Array was used to assess these genome-wide methylation patterns.
2022-01-11 | GSE179571 | GEO