The First 90 Days: Temporary Effect of Alemtuzumab on CMV Immune Reconstitution
Human cytomegalovirus (CMV) infection represents a major cause of morbidity after solid organ transplantation. Frequently, the infection arises from virus reactivation in the graft or transplant recipient during the immunosuppression phase; however, the rate of symptomatic infections and disease depend on the transplant recipient CMV serostatus before transplant: severe disease and clinically relevant infections are common conditions occurring in CMV seronegative transplant recipient receiving CMV seropositive graft (CMV D+/R−), whereas CMV seropositive transplant recipients (CMV R+) are known to be less susceptible to overt CMV infection and disease, indicating that the transplant recipient immunity, in particular the CMV specific CD4+ and CD8+ T cells, play a crucial role in keeping viral replication under control and limiting the clinical severity of the infection.1 For this reason, the assessment of CMV-specific immune reconstitution is widely used to assess on individual basis the risk of infection and the posttransplant CMV immune monitoring is also recommended from the recent CMV management guidelines for transplantation.2-6 In the recent years, the wide use in transplant settings of immunomodulatory molecules, mainly monoclonal antibodies targeting specific branches of the immune system, raised significant concerns on the long-term consequences on the immune system function and on the potential risk of opportunistic infections.7 Monoclonal antibodies in particular may have a long-term and profound inhibition on specific cell targets.8 Using cytokine flow cytometry, Ge and colleagues9 examined in 33 kidney transplant recipients the effect of alemtuzumab on CMV specific immune recovery. Alemtuzumab is a monoclonal antibody targeting the CD52 protein expressed on the surface of mature lymphocytes but not on the lymphocytic stem cells, and the use of alemtuzumab induction is particularly indicated for highly HLA-sensitized patients. Interestingly, a prior study showed that alemtuzumab has similar efficacy to basiliximab.10 Ge and colleagues show that 75% of transplant subjects recover CMV specific immunity by 2 months after alemtuzumab treatment and 95% of transplant recipients recover CMV immunity at 3 months after alemtuzumab treatment. Because alemtuzumab specifically targets mature lymphocytes, it is probable that the remaining lymphocytic stem cells not affected by alemtuzumab treatment may be able to differentiate and repopulate the immune cell repertoire within 90 days after treatment. Before this study also the antithymocyte globulin treatment was shown to have a limited impact on CMV-specific immune recovery.3 This evidence shown by Ge and colleagues support that the intravenous immunoglobulin treatment combined with rituximab desensitization and alemtuzumab induction does not impair on long term the CMV-specific immune recovery.