Causal association of circulating immune cells and lymphoma: A Mendelian randomization study

Malignant lymphoma (ML) is a group of malignant tumors originating from the lymphatic hematopoietic system. Previous studies have found a correlation between circulating immune cells and ML. Nonetheless, the precise influence of circulating immune cells on ML remains uncertain.

Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and ML risk. A total of four types of immune signatures, median fluorescence intensities, relative cell, absolute cell, and morphological parameters were included. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between circulating immune cells and the risk of ML. Sensitivity analysis was conducted using Cochran's Q test, the Mendelian randomization Egger regression intercept test, and leave-one-out analysis.

ML had a statistically significant effect on immunophenotypes. Twenty-three immunophenotypes were identified to be significantly associated with Hodgkin lymphoma risk through the IVW approach, and the odds ratio values of CD64 on CD14^- CD16⁺ monocyte [2.31, 95% confidence interval (CI) = 1.41-3.79, P1 = 0.001], IgD⁺ CD24⁺ B-cell %lymphocyte (2.06, 95% CI = 1.13-3.79, P1 = 0.018), B-cell %lymphocyte (1.94, 95% CI = 1.08-3.50, P1 = 0.027), CD24⁺ CD27⁺ B-cell %lymphocyte (1.68, 95% CI = 1.03-2.74, P1 = 0.039), and CD14⁺ CD16^- monocyte %monocyte (1.60, 95% CI = 1.15-2.24, P1 = 0.006) ranked in the top five. Eleven immunophenotypes were identified to be significantly associated with non-Hodgkin lymphoma risk, CD86 on granulocyte (2.35, 95% CI = 1.18-4.69, P1 = 0.015), CD28^-CD8⁺ T-cell absolute count (1.76, 95% CI = 1.03-2.99, P1 = 0.036), CCR2 on myeloid dendritic cell (CD24⁺ CD27⁺ B cell, 95% CI = 1.02-1.66, P1 = 0.034), CD3 on effector memory CD8⁺ T cell (1.29, 95% CI = 1.02-1.64, P1 = 0.012), and natural killer T %lymphocyte (1.28, 95% CI = 1.01-1.62, P1 = 0.046) were ranked in the top five.

This study presents compelling evidence indicating the correlation between circulating immune cells and lymphoma, thus providing guidance for future clinical research.