Relationship between antithymocyte globulin, T cell phenotypes, and clinical outcomes in pediatric kidney transplantation.

Affiliation

Shaw BI(1), Lee HJ(2), Chan C(2), Ettenger R(3), Grimm P(4), Pearl M(3), Reed EF(5), Robien MA(6), Sarwal M(7), Stempora L(1), Warshaw B(8), Zhao C(2), Martinez OM(9), Kirk AD(1)(10), Chambers ET(1)(10).
Author information:
(1)Department of Surgery, Duke University, Durham, North Carolina, USA.
(2)Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA.
(3)Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA.
(4)Department of Pediatrics, Stanford University, Stanford, California, USA.
(5)Department of Pathology, University of California, Los Angeles, California, USA.
(6)National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
(7)Department of Surgery, University of California, San Francisco, California, USA.
(8)Department of Pediatrics, Children's Healthcare Atlanta, Atlanta, Georgia, USA.
(9)Department of Surgery, Stanford University, Stanford, California, USA.
(10)Department of Pediatrics, Duke University, Durham, North Carolina, USA.

Abstract

Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Pediatric Transplant (IMPACT) study, we compared T cell phenotypes after ATG or non-ATG induction. We examined the effects of ATG on the early clinical outcomes of alloimmune events (development of de novo donor specific antibody and/or biopsy proven rejection) and infection events (viremia/viral infections). Long-term patient and graft outcomes were examined using the Scientific Registry of Transplant Recipients. After ATG induction, although absolute counts of CD4 and CD8 T cells were lower, patients had higher percentages of CD4 and CD8 memory T cells with a concomitant decrease in frequency of naïve T cells compared to non-ATG induction. In adjusted and unadjusted models, ATG induction was associated with increased early event-free survival, with no difference in long-term patient or allograft survival. Decreased CD4+ naïve and increased CD4+ effector memory T cell frequencies were associated with improved clinical outcomes. Though immunologic parameters are drastically altered with ATG induction, long-term clinical benefits remain unclear in pediatric patients.