Exploring mediating effects of B cell and monocyte in the causal relationship between diacylglycerol and trigeminal neuralgia

Changes in plasma lipidome often occur simultaneously with alterations in the immune system. The potential causal relationships between serum lipids changes and trigeminal neuralgia (TN), as well as the possibility of immune cells mediating these relationships, have not yet been understood. We conducted 2-step and 2-sample Mendelian randomization analyses using single nucleotide polymorphism data from genome-wide association studies to examine the causal relationships between genetically determined lipids levels and TN, including the intermediary impacts of immune cells. Mendelian randomization analyses revealed causal relationships between 14 lipids levels and TN, as well as between 22 immune cell phenotypes and TN. Statistically significant causal relationships were observed between 2 types of lipids (diacylglycerol (18:1_18:1), diacylglycerol (18:1_18:3)) and immune cells, including B cells (CD20 on IgD+, CD24 on IgD+ CD24+) and monocyte (CCR2 on CD14- CD16+ monocyte). The causal relationships were mediated by immune cell phenotypes to different degrees, ranging from 3.45% to 7.19%. Our study identified multiple causal relationships between various lipids levels, immune cell phenotypes and TN. We also found that the causal relationships between diacylglycerol and TN can be mediated by B cells and monocytes with specific phenotypes. These findings will contribute to our understanding of the underlying pathogenesis of TN and provide new therapeutic targets.