Antithymocyte Globulin is Associated with Mature T Cell Phenotypes and Decreased Risk of Non-EBV Infections in Transplanted Children

B. I. Shaw¹, L. Stempora¹, C. Chan¹, R. B. Ettenger², P. C. Grimm³, H. Lee¹, E. F. Reed², M. M. Sarwal⁴, B. L. Warshaw⁵, C. Zhao¹, O. M. Martinez³, A. D. Kirk¹, E. T. Chambers¹

¹Pediatrics/Surgery, Duke University, Durham, NC, ²Pediatrics, University of California, Los Angeles, Los Angeles, CA, ³Pediatrics/Surgery, Stanford University, Palo Alto, CA, ⁴Pediatrics/Surgery, University of California, San Francisco, San Francisco, CA, ⁵Pediatrics, Emory University, Atlanta, GA

Meeting: 2019 American Transplant Congress

Abstract number: 349

Keywords: Epstein-Barr virus (EBV), Induction therapy, Infection, Kidney transplantation

Session Information

Session Name: Concurrent Session: Kidney: Pediatrics II

Session Type: Concurrent Session

Date: Monday, June 3, 2019

Session Time: 4:30pm-6:00pm

Presentation Time: 5:30pm-5:42pm

Location: Room 304

*Purpose: Depletional induction therapies are known to reduce the rate of acute rejection; yet data from the US Renal Data System have shown that use of antithymocyte globulin (ATG) in children is paradoxically associated with fewer infections. ATG is known to disproportionately deplete naïve compared to memory T cells. We therefore prospectively assessed the relationship between ATG induction, T cell phenotype, and viremia in pediatric kidney transplantation.

*Methods: In a multicenter prospective NIH-funded trial, Immune Development in Pediatric Transplantation, 104 pediatric recipients were enrolled and studied for one year. Biopsy proven acute rejection and infections (defined as bacterial, viral/viremia, fungal or protozoal) were tracked clinically, and T cell subsets were defined by flow cytometry. Competing risk analysis for infection and rejection was performed by ATG induction status. T cell subsets were compared by Wilcoxon Rank-Sum tests.

*Results: 27 of 104 (26%) patients received ATG and 77 (74%) received IL-2 receptor blockade. Patients who underwent ATG induction had a lower rate of overall post-transplant events, notably a significant decrease in non-EBV related infections (Panel 1). Patients who underwent ATG induction had a more mature immune phenotype with an increase in CD4+ CCR7- CD45RA- effector memory T cells (p=0.03), a decrease in CD4+CCR7+CD45RA+ naïve T cells (Panel 2a, p=0.02), and increased PD1+ CD57- CD4+ T cells (Panel 2b, p=0.02) at 6 months post-transplant.

*Conclusions: ATG induction in pediatric patients favors a mature CD4 T cell phenotype, which correlates with fewer non-EBV infections. This advantage is not seen for EBV infections, possibly due to as an increase in CD4+ PD1+ T follicular helper cells, which are necessary for efficient maturation of B cells and EBV replication. These observations support the tailored use of ATG in pediatric kidney transplantation and provide further links between ATG induction and risk of post-transplant lymphoproliferative disorder.

To cite this abstract in AMA style:

Shaw BI, Stempora L, Chan C, Ettenger RB, Grimm PC, Lee H, Reed EF, Sarwal MM, Warshaw BL, Zhao C, Martinez OM, Kirk AD, Chambers ET. Antithymocyte Globulin is Associated with Mature T Cell Phenotypes and Decreased Risk of Non-EBV Infections in Transplanted Children [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/antithymocyte-globulin-is-associated-with-mature-t-cell-phenotypes-and-decreased-risk-of-non-ebv-infections-in-transplanted-children/. Accessed November 22, 2024.

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