Insights in Cellular and Molecular Signatures of the Small Intestinal Graft Posttransplantation: Successful, Recovered, and Rejected-A Case Series.

BACKGROUND

Intestinal transplantation is the treatment for patients with irreversible intestinal failure and complications of parenteral nutrition. Five-year graft survival is only 56%, possibly due to an imbalance in immunosuppression, aiming to prevent rejection while maintaining protection against pathogens. Studying the graft's mucosal cell populations and regulation of donor and recipient cells posttransplantation offers a unique opportunity to address this (im)balance leading to rejection.

METHODS

We performed single-cell mRNA sequencing of longitudinally sampled ileal graft biopsies from surgery up to 6 mo after transplantation, althrough the TransplantLines Biobank and Cohort Study to characterize the composition and function of donor and recipient cell populations.

RESULTS

A rapid influx of recipient immune cells was observed in the rejected transplant. Induction therapy using anti-thymocyte globulin did not achieve complete T-cell depletion. Instead, during moderate rejection, apoptotic pathways in epithelial cells preceded pathology-defined severe rejection, indicating potential prognostic information in the transcriptomic profiles.

CONCLUSIONS

This first longitudinal cellular-molecular study of the total ileal graft mucosa and recipient cells within, shows a variable clinical course and response to medication, which align with heterogeneous signatures before intestinal transplantation rejection.