Altered molecular pathways and prognostic markers in active systemic juvenile idiopathic arthritis: integrated bioinformatic analysis
Open Access
- 3 September 2021
- journal article
- research article
- Published by Association of Basic Medical Sciences of FBIH in Bosnian Journal of Basic Medical Sciences
- Vol. 22 (2), 247-260
- https://doi.org/10.17305/bjbms.2021.6016
Abstract
Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and extra-articular symptoms. While recent advances have unraveled a range of risk factors, the pathomechanisms involved in SJIA and potential prognostic markers for treatment success remain partly unknown. In this study, we included 70 active SJIA and 55 healthy control patients from the National Center for Biotechnology Information to analyze for differentially expressed genes (DEGs) using R. Functional enrichment analysis, protein-protein interaction (PPI), and gene module construction were performed for DEGs and hub gene set. We additionally examined immune system cell composition with CIBERSORT and predicted prognostic markers and potential treatment drugs for SJIA. In total, 94 upregulated and 24 downregulated DEGs were identified. Two specific modules of interest and eight hub genes (ARG1, DEFA4, HP, MMP8, MMP9, MPO, OLFM4, PGLYRP1) were screened out. Functional enrichment analysis suggested that complex neutrophil-related functions play a decisive role in the disease pathogenesis. CIBERSORT indicated neutrophils, M0 macrophages, CD8+ T cells, and naïve B cells to be relevant drivers of disease progression. Additionally, we identified TPM2 and GZMB as potential prognostic markers for treatment response to canakinumab. Moreover, sulindac sulfide, (-)-catechin, and phenanthridinone were identified as promising treatment agents. This study provides a new insight into molecular and cellular pathogenesis of active SJIA and highlights potential targets for further research.Keywords
Funding Information
- China Scholarship Council (202006210082)
- Berlin Institute of Health
This publication has 55 references indexed in Scilit:
- Application of ggplot2 to Pharmacometric GraphicsCPT: Pharmacometrics & Systems Pharmacology, 2013
- STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patientsJCI Insight, 2013
- clusterProfiler: an R Package for Comparing Biological Themes Among Gene ClustersOMICS: A Journal of Integrative Biology, 2012
- Neutrophils in the activation and regulation of innate and adaptive immunityNature Reviews Immunology, 2011
- Gene expression profiles from discordant monozygotic twins suggest that molecular pathways are shared among multiple systemic autoimmune diseasesArthritis Research & Therapy, 2011
- A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial)Annals Of The Rheumatic Diseases, 2010
- Urine Peptidomic and Targeted Plasma Protein Analyses in the Diagnosis and Monitoring of Systemic Juvenile Idiopathic ArthritisClinical Proteomics, 2010
- Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansionBlood, 2010
- CorrgramsThe American Statistician, 2002
- Serum Arginase Level in Patients with Gastric CancerJournal of Clinical Gastroenterology, 1994