Identifying the “Operational Tolerant” Pediatric Liver Transplant Recipient by Cytometry by Time-of-Flight
1Surgery, Division of Abdominal Transplantation, Stanford University, Stanford, CA
2Pediatrics, Div. Gastroenterology, Hepatology, and Nutrition, University of California, San Francisco, San Francisco, CA
3Pediatrics, Div. Gastroenterology, Hepatology, and Nutrition, Stanford University, Stanford, CA.
Meeting: 2015 American Transplant Congress
Abstract number: 240
Keywords: Liver transplantation, Pediatric, Tolerance
Session Information
Session Name: Concurrent Session: Tolerance: Clinical Studies
Session Type: Concurrent Session
Date: Monday, May 4, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 3:27pm-3:39pm
Location: Room 122-AB
Liver allografts are known to be well tolerated and indeed, some recipients of liver allografts retain stable graft function in the absence of immunosuppression. The major gap in the field is finding a method that identifies those patients who would retain healthy graft function without immunosuppression. To define an immune signature or biomarker, of recipients of liver allografts that are operationally tolerant (TOL) we utilized cytometry by time-of-flight (CyTOF, mass cytometry) to comprehensively characterize the peripheral blood mononuclear cells from recipients (n=8) of liver allografts [16.4±1.7 years (y) post-transplant, mean age 16y, mean time off IS = 10.6±2.0 y] in comparison to age-matched recipients on conventional immunosuppression (single agent tacrolimus monotherapy, IS; n=8; 13.0±1.5 y post-transplant, mean age 15y) and healthy donors (HD; n=5; mean age 18.6y). Immunosuppression was halted in the TOL group due to non-compliance, post-transplant lymphoproliferative disease or chronic EBV viremia.
Correlation analyses from mass cytometry data was performed using Citrus, a method for unsupervised identification of significant cellular populations, with cell subsets identified using hierarchical clustering of live cells using R. Cells were clustered on the basis of the expression of 22 markers. Significant changes in cell frequency were inferred using the “samr” or “glmnet” packages in R. When all three patient populations were compared, one cluster of significance, a CD4+FoxP3+CD27+CD25+ T cell population was significantly increased in the TOL patients as compared to both the IS and HD groups. When TOL and IS patients were analyzed against each other, an additional significant cell population, a CD19+CD20+CD38+CD45RA+HLA-DR+ B cell subset, was determined to be increased in TOL as compared to IS patients.
In addition to defining a potential biomarker for operational tolerance, these studies will determine those transplant recipients that can be successfully removed from immunosuppression.
To cite this abstract in AMA style:
Lau A, Vitalone M, Haas K, Shawler T, Esquivel C, Martinez O, Castillo R, Krams S. Identifying the “Operational Tolerant” Pediatric Liver Transplant Recipient by Cytometry by Time-of-Flight [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/identifying-the-operational-tolerant-pediatric-liver-transplant-recipient-by-cytometry-by-time-of-flight/. Accessed December 3, 2024.« Back to 2015 American Transplant Congress