Publications by authors named "A J Demetris"
The maintenance of stable allograft status in the absence of immunosuppression, known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multi-center, biomarker-strategy design, immunosuppression withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating immunosuppression weaning.
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- * Research on heart transplants with mismatched MHC class II revealed that graft-derived IL-33 activates tissue repair pathways in Tregs and macrophages, with a notable impact from regulating amphiregulin (Areg) expression.
- * Deleting Areg specifically in Tregs indicated that Areg promotes chronic rejection through increased fibroblast growth, suggesting that the interplay between IL-33 from fibroblasts and Tregs is crucial for advancing CR in transplanted organs.
Immunosuppression can be withdrawn from selected liver transplant recipients, although robust clinical predictors of tolerance remain elusive. The Immune Tolerance Network ITN056ST study (OPTIMAL; NCT02533180) assessed clinical outcomes and mechanistic correlates of phased immunosuppression withdrawal (ISW) in nonautoimmune, nonviral adult liver transplant recipients. Enrolled subjects were ≥3 years posttransplant with minimal/absent inflammation or fibrosis on a screening liver biopsy.
View Article and Find Full Text PDFThe XVI-th Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from 19th-23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30 anniversary of the first Banff Classification, pre-meeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis.
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- There is a complex difference between autoimmune and alloimmune reactions in liver transplant patients, particularly involving an under-recognized form of graft rejection called plasma cell-rich rejection (PCRR).
- PCRR can lead to serious complications like advanced liver damage and transplant failure if not treated quickly, highlighting the need for effective detection methods.
- This study reviews potential blood and tissue biomarkers for diagnosing and monitoring PCRR in liver transplant recipients, as well as discusses related biomarkers from other medical conditions that might be applicable.