Characterization of T cell immunophenotypes in intestinal transplantation: A pilot study
Introduction
Intestinal transplantation (ITx) is a lifesaving procedure for patients with irreversible intestinal failure who have complications of parenteral nutrition, an inability to adapt to the quality-of-life limitations posed by intestinal failure, and/or a high risk of death if the native intestine is not removed [1]. Modest improvements have been made in early graft survival rates over the past decade, but rates of allograft loss beyond one year have not improved [2]. A significant barrier to successful ITx is acute cellular rejection (ACR). ACR continues to affect almost 40% of ITx recipients in the first year after transplantation [3] with potentially devastating consequences. ACR also remains an important cause of late allograft loss [4].
In the setting of intestinal allograft dysfunction, a major challenge is the differentiation of ACR from infectious enteritis. Infectious enteritis is a common cause of allograft dysfunction, occurring in up to three quarters of pediatric ITx recipients [5]. Although the gold standard for diagnosis of ACR is endoscopy with biopsy to identify key histopathologic findings [6], there are inherent disadvantages to endoscopy. Histopathology obtained from endoscopy is subject to sampling and interpretation error [7], with newer grading scores being proposed [8]. In addition, endoscopy is associated with higher risks of complications in pediatric ITx recipients [9] as well as a significant burden of cost [10]. Thus, there remains a clear need for a non-invasive means to discriminate between ACR and infectious enteritis.
Although multiple prior attempts to develop non-invasive biomarkers of immune monitoring in ITx have been suboptimal [[11], [12], [13], [14]], immunophenotyping of T cells has been shown to be a useful, non-invasive method of predicting ACR in pediatric ITx [15,16]. Peripheral blood mononuclear cells (PBMCs), including T cells, offer a unique window through which the recipient's immune response to transplanted tissue can be monitored non-invasively. These cells are present in the peripheral blood after allo-endothelial-cell contact in the allograft due to recirculation. Immunophenotyping of specific T cell subsets have also been associated with ACR in pediatric liver transplantation [17,18] and adult renal transplantation [19].
We performed a cross-sectional, single center, pilot study to monitor peripheral blood T cell immunophenotypes at various time intervals following ITx and across clinical states (ACR, infectious enteritis, and normal baseline stability).
Section snippets
Objectives
The objectives of this study were to [1] characterize differences in the peripheral blood T cell immunophenotype of ITx recipients in normal samples collected late versus early after ITx and [2] characterize differences in the peripheral blood T cell immunophenotype associated with episodes of ACR and infectious enteritis.
Study design
This was a prospective, cross-sectional study of ITx recipients transplanted from 2000 to 2016. Samples were collected from 2011 to 2017. The study was approved by the University of California, Los Angeles (UCLA) institutional review board, IRB #12-001231.
Study population and sample collection
Informed consent was obtained from patients and/or their parents at the time of enrollment. All patients followed by the UCLA Intestinal Transplant Program who received an ITx, with or without a liver allograft, were eligible for the study.
Study population
The study population was comprised of 38 patients: 31 ITx recipients and 7 intestinal failure control patients. The ITx cohort included 26 children and 5 adults. Five of the patients were re-ITx recipients; 87% of ITx recipients had a liver-inclusive allograft. The most common underlying etiology of intestinal failure was surgical short bowel syndrome in the ITx recipients, with the most common diagnosis of gastroschisis (n = 8). Comparatively, the most common underlying etiology of intestinal
Discussion
The study reported herein features immunophenotyping data from a relatively large cohort of ITx recipients at a single center. ITx is an uncommon procedure, reserved for a subset of intestinal failure patients who have developed complications of parenteral nutrition. The most recent data from OPTN/SRTR states that, as of 2016, there were almost 1200 ITx recipients living with a functioning allograft, with a total of 147 intestinal transplants performed in that year [3]. Thus, clinical research
Acknowledgements
The authors would like to thank the UCLA Intestinal Transplantation Team, UCLA Immune Assessment Core (Gemalene Sunga, Fadi Kandarian, Diana Arango-Saenz), UCLA Immunogenetics Center Biorepository (Victoria Groysberg, Andrea Alvarez), and Dr. Martin G. Martin. This research was supported by NIH National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881.
Funding
This work was supported by the UCLA Children's Discovery and Innovation Institute Harry Winston Fellowship Award, UCLA Children's Discovery and Innovation Institute Today's and Tomorrow's Children Fund, and the UCLA Clinical and Translational Science Institute Scholar Award.
Declarations of interest
None.
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