Childhood Emotional Neglect, Self-Criticism, and Meaning in Life Among Adults Living in Therapeutic Communities.

UNLABELLED: This study investigated the cytokine profiles and expression patterns of chromosome 21 genes in Saudi Arabian children with Down syndrome (DS) to identify molecular drivers of immune dysregulation and pulmonary complications. This case-control study enrolled 116 children with DS and 60 healthy controls. Cytokine levels Interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor-alpha (TNF-α), Monocyte Chemoattractant Protein-1 (MCP-1), IL-1β, Interferon-gamma (IFN-γ), and Transforming Growth Factor-beta (TGF-β) were measured at baseline and after lipopolysaccharide (LPS) stimulation using the Meso Scale Discovery (MSD) V-PLEX platform. Gene expression analysis was performed on a panel of immune-related (Small Ubiquitin-Like Modifier 3 (SUMO3), Runt-Related Transcription Factor 1 (RUNX1), Autoimmune Regulator (AIRE), and Regulator of Calcineurin 1 (RCAN1)) and pulmonary genes (DNA Methyltransferase 3 Like (DNMT3L), Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1 A (DYRK1A), miR-let-7c-5p, miR-99a-5p, VEGF, and Integrin Subunit Beta 2 (CD18) located on chromosome 21 using quantitative real-time PCR (qRT-PCR). Children with DS exhibited elevated levels of pro-inflammatory cytokines (IL-6, IL-8, VEGF, and TNF-α) and the anti-inflammatory cytokine MCP-1 compared to controls, both at baseline and after LPS stimulation (p < 0.05). Gene expression analysis revealed upregulation of immune-related genes (SUMO3, RUNX1, AIRE, and RCAN1) and pulmonary genes (DNMT3L, DYRK1A, miR-Let-7c-5p, miR-99a-5p, VEGF, and CD18) in the DS group. SUMO3 and AIRE emerged as strong predictors of DS, while miR-Let-7c-5p, miR-99a-5p, and VEGF revealed potential as biomarkers for pulmonary complications. receiver operating characteristic (ROC) analysis identified SUMO3 (AUC: 0.935) and AIRE (AUC: 0.890) as strong predictors of the DS immune phenotype. Furthermore, miR-let-7c-5p (AUC: 0.966), miR-99a-5p (AUC: 0.913), and VEGF (AUC: 0.944) demonstrated superior diagnostic accuracy as potential biomarkers for DS-associated pulmonary abnormalities. This study provides a comprehensive insight into the immune dysregulation and genetic predisposition in Saudi Arabian children with DS. The findings highlight potential biomarkers (IL-6, IL-8, VEGF, TNF-α, MCP-1, SUMO3, RUNX1, DNMT3L, DYRK1A) and therapeutic targets for personalized medicine approaches to manage immune dysfunction and respiratory complications in this population.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-026-04879-9.