مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Deciphering shared and distinct molecular mechanisms in pediatric and adult Systemic Lupus Erythematosus: A Comparative gene expression and pathway analysis
Deciphering shared and distinct molecular mechanisms in pediatric and adult Systemic Lupus Erythematosus: A Comparative gene expression and pathway analysis
Roghayeh Ramezani,1Shirin Farivar,2,*Masoud Tohidfar,3
1. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University 2. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University 3. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University
Introduction: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease that manifests differently in pediatric and adult patients. While both groups share core disease mechanisms, emerging evidence suggests potential differences in gene expression profiles and affected biological pathways. Identifying key differentially expressed genes (DEGs) in pediatric and adult SLE and analyzing their shared and unique pathways can enhance our understanding of disease pathophysiology and support personalized therapeutic approaches. This study aims to compare differentially expressed genes in pediatric and adult SLE patients and explore their involvement in biological pathways.
Methods: Four microarray datasets were retrieved and analyzed using RStudio: GSE61635 and GSE20864 for adult SLE, and GSE11909 and GSE46907 for pediatric SLE. Data preprocessing included background correction, normalization, and batch effect removal. Differential gene expression analysis was performed using the limma package, and DEGs were identified based on an adjusted p-value < 0.05 and log fold-change (logFC) > 1. The top 10 upregulated and downregulated genes were identified for each group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to determine the biological pathways associated with these genes and their overlap between the two age groups.
Results: The analysis revealed distinct gene expression patterns in pediatric and adult SLE patients. In adults, key interferon-stimulated genes (ISGs) such as ISG15, HERC5, USP18, OASL, IFIT3, IFI44, and IFI6 were highly upregulated, indicating robust interferon-mediated immune activation. These genes play pivotal roles in antiviral defense and immune regulation, suggesting an intensified inflammatory response contributing to disease severity in adult patients. Similarly, pediatric patients exhibited upregulation of interferon-related genes including IFI27, SIGLEC1, IFI44L, IFIT1, and RSAD2, highlighting a central role of interferon signaling in childhood SLE. Notably, the shared upregulation of IFI44 and IFI44L underscores a common interferon-driven immune dysregulation across both groups. Furthermore, the elevated expression of USP18, a negative regulator of interferon signaling, in both adults and children suggests a compensatory mechanism aimed at modulating excessive immune activation.
In contrast, differential patterns emerged among downregulated genes. Adult SLE patients demonstrated decreased expression of SLC4A1, KLF1, SLC25A39, and MYL4, genes implicated in erythropoiesis and red blood cell membrane integrity, potentially contributing to anemia and altered oxygen transport. Meanwhile, pediatric patients showed downregulation of ATP8B1, LRP1B, KCNK3, and FCER1A, genes involved in ion transport and cellular homeostasis, indicating distinct metabolic disruptions in childhood SLE. These differences suggest that, while both age groups experience metabolic perturbations, the underlying cellular mechanisms are age-specific and may influence disease progression and clinical manifestations.
Pathway analysis further revealed both shared and distinct biological processes between the two groups. Both pediatric and adult SLE patients exhibited activation of type I interferon signaling and general immune response pathways. However, adult patients showed enrichment in TNF signaling and oxidative stress response pathways, while pediatric patients demonstrated a stronger signature of neutrophil activation and cytokine production. These findings suggest that, although interferon-driven inflammation is a common hallmark of SLE, additional age-dependent mechanisms contribute to disease severity and progression in pediatric and adult populations.
Conclusion: This study highlights both shared and age-specific gene expression patterns and biological pathways in pediatric and adult SLE patients. The findings suggest that while interferon-driven immune dysregulation is central to SLE in both age groups, unique molecular signatures contribute to disease heterogeneity. The identification of USP18 as a common upregulated gene strengthens its potential as a universal biomarker. Additionally, distinct downregulated genes hint at age-related differences in immune regulation and metabolic responses. These insights could inform the development of tailored diagnostic and therapeutic strategies for SLE patients based on age-specific molecular characteristics. Further validation through experimental studies and larger patient cohorts is essential to confirm these findings and enhance precision medicine approaches in SLE.