Digital cytometry of leukocyte landscapes reveals shared correlates of rejection across organ transplants

In all organs, rejection correlated with an increase in DLEs designated as classically activated macrophages and a decrease in DLEs designated regulatory T cells. T cell-mediated rejection (TCMR) was associated with a massive increase in otherwise rare T cell DLEs designated memory-activated CD4 and Tγδ, as well as follicular-helper CD4 and CD8. TCMR also had increased DLE designated plasma cells, compatible with a role for the B cell lineage in antigen presentation in TCMR.

Antibody-mediated rejection (ABMR) in kidney and heart transplant biopsies correlated with increased DLEs representing activated mast cells, activated NK cells, and monocytes. Some findings were validated by single-cell/nucleus RNAseq data from kidney and liver biopsies. Conclusion.

The shared correlations of DLEs with rejection in all organs - e.g. CD4ma with TCMR and activated mast cells with ABMR - suggest novel aspects of rejection. These findings can guide the search for the in vivo leukocytes that correspond with the digital entities and potential clinical applications.