Impact of rituximab-based desensitization on T cell-mediated rejection in ABO-incompatible liver transplantation

Abstract Purpose Rituximab-based desensitization has enabled successful ABO-incompatible (ABO-I) liver transplantation (LT) by preventing antibody-mediated rejection (AMR). However, its effect on T cell-mediated rejection (TCMR) remains unclear. We conducted a comparative analysis between ABO-compatible (ABO-C) and ABO-I LT to evaluate the effects of rituximab-based desensitization on TCMR. Methods We retrospectively analyzed 45 LT recipients (32 ABO-C and 13 ABO-I recipients) treated with basiliximab-based immunosuppression. The ABO-I group additionally received rituximab-based desensitization therapy. The lymphocyte subpopulations, rejection, adverse events, and outcomes were assessed. Results AMR was not observed in either group. TCMR occurred within 4 weeks post-transplantation in 0% of ABO-C cases and 38.5% of ABO-I cases ( P = 0.0011). In ABO-C, a significant increase in B cells (CD19+) was observed within the first week, whereas in ABO-I, B cells remained depleted and an increase in T cells (CD3+) was observed. In all the ABO-I cases, TCMR occurred under suppressed CD25 + conditions. Adverse events were comparable between the groups. The 1-year survival rates for the ABO-C and ABO-I groups were 96.9% and 100%, respectively. Conclusion Rituximab-based desensitization in ABO-I LT is associated with an increased incidence of early TCMR. Rituximab-induced B-cell depletion may promote T-cell activation through an IL-2-independent pathway, potentially contributing to increased TCMR.