High-dimensional profiling of pediatric immune responses to solid organ transplantation

Abstract

Solid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ~25% of allograft recipients experience acute rejection within the first 12 months after transplant. Our ability to detect rejection early and to develop less toxic immunosuppressive agents is hampered by an incomplete understanding of the immune changes associated with rejection, particularly in the pediatric population. Here we used high-dimensional single-cell proteomic technologies (CyTOF) to generate the first detailed, multi-lineage analysis of the peripheral blood immune composition of pediatric solid organ transplant recipients. We report that the organ transplanted impacts the immune composition post-transplant. When taking these allograft-specific differences into account, we further observed that differences in the proportion of subsets of CD8 and CD4 T cells were significantly associated with allograft health. Together, these data form the basis for mechanistic studies into the pathobiology of rejection to develop less invasive tools to identify early rejection and new immunosuppressive agents with greater specificity and less toxicity.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by awards from the NIH (UO1 AI104342 [C.O.E.], U01 AI1359590 [S.M.K.]), the Stanford Maternal and Child Health Research Institute [M.R.], the Stanford Transplant and Tissue Engineering Center of Excellence [M.R.] and the Stanford University Jackson Vaughan Critical Care Research Fund [M.R.]. M.A. is supported by the Stanford Immunology Training Grant T32 AI007290_37.

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institutional review boards of the following institutions have ethical approval for this work: Lucile Packard Childrens Hospital Stanford, CA; University of Texas Southwestern Medical Center, Dallas, TX; University of Pittsburgh Medical Center Childrens Hospital, Pittsburgh, PA; University of California, Los Angeles, CA; University of Miami Health System, Miami, FL; Medstar Georgetown Transplant Institute, Washington, DC; Cincinnati Childrens Hospital Medical Center, University of Cincinnati, Cincinnati, OH

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Yes

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Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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