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

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 trans-plant. 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.

Automated summary

Solid organ transplant is a life-saving therapy for children with end-stage organ diseases, but a significant proportion of recipients experience acute rejection. This study analyzed the immune composition of pediatric solid organ transplant recipients using high-dimensional mass cytometry, and found that the type of organ transplant strongly influences the post-transplant immune profile. Changes in the proportion of different T cell subpopulations are associated with graft health. These findings provide a basis for further understanding and developing new immunosuppressive agents.