Causal Implication of CD52-Driven Immune Dysregulation in Sarcopenic Obesity: Integrating Mendelian Randomization and Multiomics Profiling

Saiyare Xuekelati,1 Yilihamu Abulitifu,2 Zhuoya Maimaitiwusiman,3 Lei Xu,1 Shuke Guo,1 Qihong Xu,1 Jiayu Ke,1 Hongmei Wang3,4 1Graduate School, Xinjiang Medical University, Urumqi, People’s Republic of China; 2Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 3Second Department of Comprehensive Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 4Xinjiang Medical University, Urumqi, People’s Republic of ChinaCorrespondence: Hongmei Wang, Email [email protected]: Sarcopenic obesity patients are likely to develop exacerbated metabolic dysfunction, while the mechanism linking sarcopenia and obesity is still unclear. This study aims to explore hub genes and immune-metabolic dysregulation related to the molecular pathogenesis of sarcopenia and obesity.Methods: We used a public Gene Expression Omnibus (GEO) dataset to identify hub genes associated with sarcopenia and obesity. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI), differentially expressed gene (DEG) analysis, GO/KEGG functional enrichment analyses and immune cell infiltration analysis were conducted to identify hub genes. Subsequently, these hub genes underwent multi-level validation.Results: Integrated bioinformatics analysis identified 16 shared hub genes linked to the sarcopenia–obesity nexus. These genes were mainly enriched in immune-related pathways, as supported by immune infiltration profiling. External validation in independent cohorts confirmed CD52 as a common and central gene in both sarcopenia and obesity datasets, showing significant associations with immune cell characteristics. Mendelian randomization analysis indicated potential causal links between genetically predicted CD52 levels and reduced hand grip strength as well as increased body mass index, and these results were further supported by PCR assays in clinical samples.Conclusion: The integrative analysis indicates that CD52 may function as a novel immunometabolic mediator in SO pathogenesis, underscoring its potential as a candidate biomarker for further study.Keywords: Sarcopenia, obesity, bioinformatics, immune cell infiltration, Mendelian randomization