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

Mahil Rao; Meelad Amouzgar; James T Harden; M Gay Lapasaran; Amber Trickey; Brian Armstrong; Jonah Odim; Tracia Debnam; Carlos O Esquivel; Sean C Bendall; Olivia M Martinez; Sheri M Krams

doi:10.1016/j.xcrm.2023.101147

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

Cell Rep Med. 2023 Aug 15;4(8):101147. doi: 10.1016/j.xcrm.2023.101147. Epub 2023 Aug 7.

Authors

Affiliations

¹ Department of Pediatrics, Division of Pediatric Critical Care Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Transplant Immunology Lab, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
² Immunology Graduate Program, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
³ Transplant Immunology Lab, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Immunology Graduate Program, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
⁴ Transplant Immunology Lab, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
⁵ Department of Surgery, Division of Abdominal Transplant Surgery, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
⁶ Rho, Inc., Durham, NC, USA.
⁷ National Institutes of Health, Bethesda, MD, USA.
⁸ Transplant Immunology Lab, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Surgery, Division of Abdominal Transplant Surgery, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
⁹ Program in Immunology, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
¹⁰ Transplant Immunology Lab, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Surgery, Division of Abdominal Transplant Surgery, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Program in Immunology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
¹¹ Transplant Immunology Lab, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Surgery, Division of Abdominal Transplant Surgery, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Program in Immunology, Stanford University School of Medicine, Palo Alto, CA 94304, USA. Electronic address: smkrams@stanford.edu.

Abstract

Solid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ∼33% of allograft recipients experience acute rejection within the first year after transplant. Our ability to detect early rejection is hampered by an incomplete understanding of the immune changes associated with allograft health, particularly in the pediatric population. We performed detailed, multilineage, single-cell analysis of the peripheral blood immune composition in pediatric solid organ transplant recipients, with high-dimensional mass cytometry. Supervised and unsupervised analysis methods to study cell-type proportions indicate that the allograft type strongly influences the post-transplant immune profile. Further, when organ-specific differences are considered, graft health is associated with changes in the proportion of distinct T cell subpopulations. Together, these data form the basis for mechanistic studies into the pathobiology of rejection and allow for the development of new immunosuppressive agents with greater specificity.

Trial registration: ClinicalTrials.gov NCT02182986.

Keywords: CyTOF; allograft; pediatric; rejection; transplantation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Child
Humans
Immunity
Kidney Diseases*
Kidney Transplantation*
Organ Transplantation*
Transplantation, Homologous

Associated data

ClinicalTrials.gov/NCT02182986

Abstract

Publication types

MeSH terms

Associated data

Grants and funding