Short-term mycophenolic acid withdrawal is associated with temporal changes in immune cell composition in...

Short-term mycophenolic acid (MPA) withdrawal is common in kidney transplant recipients with severe infections and was extended during the COVID-19 pandemic to improve vaccine immunogenicity, yet its effects on immune cell dynamics remain mechanistically understudied.

We performed high-dimensional flow cytometry combined with unsupervised computational clustering to analyze longitudinal peripheral blood mononuclear cell samples from kidney transplant recipients who received mRNA-1273 vaccination. Samples were collected before and after a 5-week temporary MPA discontinuation, and the results were compared with those of vaccinated patients maintained on standard triple immunosuppression.

Compared with continued triple immunosuppression (N = 13), MPA withdrawal (N = 11) was associated with temporal shifts in major immune compartments, including increases in the frequencies of CD4⁺ and CD8⁺ T cells (P = 0.039 and P = 0.001, respectively), as well as decreases in the frequencies of monocytes (P = 0.014) and B cells (P = 0.023). These changes were accompanied by increased relative frequencies of specific T-cell subsets, including CD8⁺ TEMRA CD38⁺ cells (P = 0.011) and early activated memory CD4⁺ T cells (P = 0.023). With increasing time since transplantation, these longitudinal patterns attenuated. Older patient age was associated with lower overall monocyte frequencies, though it did not influence their temporal trajectories. Although exploratory analyses showed subset differences between seroconverters and non-seroconverters after vaccination, no major compartment or individual subset was predictive in regression models.

Short-term MPA withdrawal was associated with selective temporal immune shifts, including increased relative frequencies of CD4⁺/CD8⁺ T-cell subsets and decreased relative frequencies of monocyte and B-cell subsets. Effects varied by time since transplantation and age, reflecting heterogeneous immune reconstitution. High-dimensional profiling enabled detailed analysis of major and rare immune populations, highlighting its value in mechanistic transplantation studies.