Causal Association Between Inflammatory Proteins, Inflammatory Cells, and Cauda Equina Syndrome: A Two-Sample...

Recent studies have shown that inflammation plays a crucial role in the progression of cauda equina syndrome (CES). However, the exact cause-and-effect relationship between them is still unclear.

We used CES data from the FinnGen genome-wide association study (GWAS), containing 329 cases and 408,351 control patients. Inflammatory proteins data were obtained from a large scale GWAS of 14,828 European ancestry participants, and inflammatory cells data were obtained from a GWAS summary of 3757 Sardinians. We chose inverse variance weighted as the main method and the Cochrane Q test to assess heterogeneity in the results. The MR-Egger intercept test and MR pleiotropy residual sum and outliers test were used to evaluate the horizontal pleiotropy, and sensitivity analysis was performed by leave-one-out analysis.

We examined robust associations between inflammatory proteins, inflammatory cells, and CES using Mendelian randomization. Two inflammatory proteins and 12 inflammatory cells were found as risk factors for CES: IL-8 and PD-L1; and basophil plasmacytoid dendritic cell, CD86+plasmacytoid dendritic cell, CD62L-plasmacytoid dendritic cell, CD39+secreting Treg, IgD+CD38-B cell, switched memory B cell, IgD+CD24+B cell, CD62L+dendritic cell, CD4+T cell, γδ T cell, and CD33dim HLA DR-myeloid cell. Two inflammatory proteins and 7 inflammatory cells were found as protective factors for CES: IL-10RA and CCL25; and transitional B cell, terminal differentiation double negative T cell, CD28-CD127-CD25++CD8br T cell, IgD+CD38br B cell, CD28+CD45RA-CD8br Treg, IgD+CD38-naive B cell, and granulocyte. Heterogeneity and pleiotropy analysis confirmed the reliability of the results. Our study reveals the causal relationship between inflammatory proteins, inflammatory cells, and CES, offering new insights for the development of future therapeutic drugs and early warning indicators.

Our findings extend genetic research to causal analysis between inflammatory proteins, cells, and CES. We found 2 proteins and 12 cells as risk factors and 2 proteins and 7 cells as protective factors. Further investigations are needed to verify whether these inflammation markers can be used to prevent or treat CES.