Influence of Altered Immune-Inflammatory Axis on the Risk of Osteomyelitis and Its Network Interaction Effect in...

Background: Osteomyelitis (OM) is a severe bone infection with rising incidence rates, particularly among elderly and diabetic patients. The immune-inflammatory axis is implicated in OM pathogenesis, but its complex interplay remains poorly defined. This study aims to explore the causal relationships between immunophenotypes, plasma inflammatory proteins, and OM using Mendelian randomization (MR) and bioinformatics. Methods: Utilizing publicly available genetic data, we undertook a series of quality control measures to identify instrumental variables (IVs) associated with exposure. Subsequently, we conducted MR using inverse variance weighting to explore the causal relationships between immunophenotypes, plasma inflammatory proteins, and OM. Bioinformatics tools were applied to explore the functional enrichment and protein-protein interaction networks of the implicated genes. Results: The MR analysis identified 13 immune cell phenotypes and 2 plasma inflammatory proteins associated with risk of OM. Notably, higher levels of HLA DR on plasmacytoid dendritic cells, memory B cell absolute counts, and CD8dim T cell percentages were associated with increased OM risk. Additionally, elevated levels of CD6 and IL-12 subunit B were correlated with OM risk. Bioinformatics analysis revealed the enrichment of related genes in immune-related pathways and highlighted the complex interaction networks of the implicated proteins. Conclusions: This study provides novel insights into the immune-inflammatory axis in OM and identifies potential biomarkers for risk assessment. The findings warrant further validation in diverse populations and pave the way for developing targeted preventive and therapeutic strategies for OM.