Long-term cell monitoring of kidney recipients after an antilymphocyte globulin induction with and without steroids

Abstract

Background: Because of several side effects, the corticosteroid usage has been minimized in kidney transplantation. The increased acute rejection episodes associated with their withdrawal may counterbalance with induction treatment using polyclonal antilymphocyte globulin (ALG). The effects of ALG on blood cell phenotype have already been the subject of several reports. However, to date, no data are available concerning the comparison of blood phenotype when ALG is given with or without steroids and no gene profiling study has been performed.

Methods: We report here on a longitudinal blood cell analysis of a selected cohort of kidney recipients enrolled in a randomized study of steroid avoidance or withdrawal (during 6 months) during ALG induction.

Results: In the two groups, ALG quickly and massively depleted all the T cells and natural killer cells, but not B cells. Interestingly, the lymphopenia-driven homeostatic proliferation of CD4 and CD8T cells strongly differed with persistent low CD4 (including CD25CD4) T-cell counts. Effector memory CD8T cells reappeared rapidly. ALG induced apoptosis-associated molecules and increased myeloid cell genes. However, few genes were found differentially expressed with a low fold ratio between the two groups during and at distance of corticotherapy.

Conclusion: Thus initial steroid avoidance or withdrawal associated with ALG induction has a weak influence on phenotype and transcriptional pattern of blood leukocytes. In contrast, ALG therapy induces an early and strong depletion of all T-cell subsets with contrasted long-lasting homeostatic regulation.