Dyslipidemia is associated with monocyte lipid metabolic reprogramming in Guillain-Barré syndrome

GBS (Guillain-Barré syndrome) is an acute immune-mediated peripheral neuropathy whose pathological mechanisms remain incompletely understood. Our study aimed to explore the intrinsic link and potential mechanisms between circulating dyslipidemia and immune metabolic remodeling of monocytes in GBS. Clinical data from 163 patients diagnosed with classic GBS and 169 healthy controls were analyzed to examine the correlations between their lipid profiles and immune cell features. Leveraging our team's previously published single-cell RNA sequencing (scRNA-seq) dataset for GBS, we characterized the subpopulations, functional features, and differentiation trajectories of peripheral blood monocytes. Furthermore, through transcriptional regulatory network analysis, we identified key transcription factors governing these processes. Compared to healthy controls, GBS patients displayed a distinct dyslipidemia characterized by elevated triglycerides (TG), very low-density lipoprotein (VLDL), and residual cholesterol (RC), but decreased high-density lipoprotein (HDL) and apolipoprotein A1 (APOA1). This lipid profile coincided with higher monocyte counts in peripheral blood, suggesting a synergistic relationship. The scRNA-seq analysis results indicate that the composition of peripheral blood monocyte subsets in GBS patients undergoes fundamental remodeling. This is characterized by a significant expansion of CD14⁺CD163⁺ monocytes lipid metabolism-active monocytes and pro-inflammatory CD14⁺CD169⁺ monocytes, while the proportion of classical monocytes sharply decreases. Pseudo-time trajectory analysis revealed a differentiation pathway from classical monocytes to CD14⁺CD163⁺ monocytes via CD14⁺CD169⁺ and intermediate monocytes. This pathway was characterized by an initial increase followed by a decrease in pro-inflammatory activity, coupled with a progressive enhancement in lipid metabolism activity. Transcriptional network analysis identified CEBPB as a core transcription factor potentially associated with the phenotypic conversion of monocyte subsets, likely mediated by synergistic regulation of genes involved in lipid metabolism and cell differentiation. In summary, GBS is characterized by synergistic dyslipidemia and monocyte remodeling. The pathological signature involves lipid metabolic reprogramming in the CD14⁺CD163⁺ monocytes and pro-inflammatory phenotypes in the CD14⁺CD169⁺ monocytes. The transcription factor CEBPB is associated with this phenotypic conversion by regulating lipid metabolism and differentiation genes, revealing molecular targets for precise GBS diagnosis and therapy.