Metabolic syndrome and inborn errors of immunity: A plausible connection

Inborn errors of immunity (IEI), traditionally known as primary immunodeficiencies, are genetically driven disorders that impair immune function. Emerging evidence suggests a strong connection between IEI and metabolic syndrome, including obesity, insulin resistance, and cardiovascular diseases, highlighting the complex interplay between immune and metabolic pathways. This review focuses on how changes in key immune regulatory genes can lead to both immune dysfunction and metabolic problems. Genome Wide Association Studies (GWAS) and Next Generation Sequencing (NGS) have identified numerous genetic variants that link immune and metabolic dysregulation. Both immune system dysfunction and metabolic imbalances are associated with mutations in several key genes such as STAT3, NLRP3, and FOXP3. Pharmacological interventions targeting inflammatory pathways, such as cytokine inhibitors and inflammasome modulators, offer promising therapeutic strategies to address both aspects of these intertwined conditions. Moreover, lifestyle modifications, including anti-inflammatory diets and physical activity, are essential components of a comprehensive approach to mitigate inflammation and improve metabolic outcomes. Advances in genomic profiling drive precision medicine, enabling the tailoring of treatments based on individual genetic variants, optimizing therapy for both immune and metabolic dysfunction. Personalized risk assessments incorporating genetic data further refine preventive strategies for metabolic syndrome. This cited approach underscores the importance of a holistic, integrated approach to unraveling the shared mechanisms of immune and metabolic dysregulation, offering insights into novel diagnostic and therapeutic strategies for these multifactorial disorders.