Rohan et al at the Medical University of South Carolina in Charleston, SC, recently evaluated the first 22 renal transplant recipients to receive clinical immune monitoring with donor-reactive T-cytotoxic memory cells. This cell type determines the likelihood of rejection in the Pleximark test. Increased donor-reactivity was associated with renal allograft rejection with a sensitivity of 83% and a negative predictive value of 91%. This increased reactivity also correlated with (r=0.453, p=0.03) with graft dysfunction measured with serum creatinine…....

Reference: Rohan VS, Soliman KM, Alqassieh A, Alkhader D, Pate N, Nadig SN. Renal allograft surveillance with allospecific T-cytotoxic memory cells. Ren Fail. 2020 Nov;42(1):1152-1156. doi: 10.1080/0886022X.2020.1846054. PMID: 33203287.

Kroemer et al at Georgetown-Medstar Transplant Institute in Washington, DC, recently reported the first ever intestine transplant recipient to show operational tolerance or a stable rejection-free status without immunosuppression. Phenotypic analysis of peripheral blood lymphocytes revealed an increase in circulating T-regulatory cells. This patient also demonstrated immunological quiescence toward donor alloantigens. Immunological reactivity toward other antigens was preserved. These functional tests were performed at Plexision. Specifically, donor-reactive T-cytotoxic memory cells and donor-specific antigen presenting B-cells and monocytes were greatly reduced. T-cell reactivity to cytomegalovirus and mitogens was unaffected.

Reference: Kroemer A, Khan K, Kaufman SS, Kang J, Weiner J, Duttargi A, Belyayev L, Ashokkumar C, Sindhi R, Timofeeva OA, Zasloff M, Matsumoto CS, Fishbein TM. Operational tolerance in intestinal transplantation. Am J Transplant. 2020 Jul 28. doi: 10.1111/ajt.16224. Online ahead of print. PMID: 32721092

Sanchez-Fueyo et al at King’s College Hospital in London, UK, assessed the safety of infusing two doses of ex-vivo-expanded T-regulatory cells (Tregs) to liver transplant recipients. Treg infusions can provide anti-rejection effect with fewer side effects than small molecule immunosuppressants, and reduce the need for these immunosuppressants. No adverse events were reported in this study. Immunophenotyping revealed an increase in circulating Tregs for up to a month after infusion following the higher dose infusion of 3-4.5 million Tregs/kg. In these patients, donor-specific T-cytotoxic memory cells declined steadily across three serial measurements conducted pre-infusion and at 1 week and 1 month after infusion. No changes were seen in reactivity to non-identical cells. The lower dose Treg infusion had no effect on donor-reactive T-cytotoxic memory cells. Thus, immune cell function assessment may help to evaluate the effect of cell therapy in transplant patients.

Reference: Sánchez-Fueyo A, Whitehouse G, Grageda N, Cramp ME, Lim TY, Romano M, Thirkell S, Lowe K, Fry L, Heward J, Kerr A, Ali J, Fisher C, Lewis G, Hope A, Kodela E, Lyne M, Farzaneh F, Kordasti S, Rebollo-Mesa I, Jose Lozano J, Safinia N, Heaton N, Lechler R, Martínez-Llordella M, Lombardi G. Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation. Am J Transplant. 2020 Apr;20(4):1125-1136. doi: 10.1111/ajt.15700. Epub 2020 Feb 3.PMID: 31715056

Soltys and Fox et al transplanted human hepatocytes in two patients with urea cycle defects. Retrospective immune monitoring was performed to assess the adequacy of immunosuppression. Early graft loss in both cases was accompanied by an increase in rejection-risk measured with donor-specific CD154+T-cytotoxic memory cells. Lymphocyte depleting induction immunosuppression was used in the next patient who received hepatocyte transplantation for phenylketonuria. Biochemical improvement of disease markers was confirmed in supervised follow-up for several months. In serial monitoring, rejection-risk measured with donor-reactive T-cells increased as follow-up became inconsistent and the graft was lost. The authors concluded that serial monitoring of rejection-risk could facilitate the management of immunosuppression in this type of cell transplant.

Reference: Soltys KA, Setoyama K, Tafaleng EN, Soto Gutiérrez A, Fong J, Fukumitsu K, Nishikawa T, Nagaya M, Sada R, Haberman K, Gramignoli R, Dorko K, Tahan V, Dreyzin A, Baskin K, Crowley JJ, Quader MA, Deutsch M, Ashokkumar C, Shneider BL, Squires RH, Ranganathan S, Reyes-Mugica M, Dobrowolski SF, Mazariegos G, Elango R, Stolz DB, Strom SC, Vockley G, Roy-Chowdhury J, Cascalho M, Guha C, Sindhi R, Platt JL, Fox IJ. Host conditioning and rejection monitoring in hepatocyte transplantation in humans. J Hepatol. 2017 May;66(5):987-1000. doi: 10.1016/j.jhep.2016.12.017. Epub 2016 Dec 24. PMID: 28027971