Post-transplant lymphoproliferative disorder associated with immunosuppressive therapy for renal transplantation in rhesus macaques (Macaca mulatta)

• Type of Material: Article
• Authors: Eugenia Page, Emory University; Cynthia L. Courtney, Emory University; Prachi Sharma, Emory University; Jennifer Cheeseman, Emory University; Joe Jenkins, Emory University; Elizabeth Strobert, Emory University; Stuart Knechtle, Emory University
• Language: English
• Date: 2013-11-01
• Publisher: Elsevier GMBH, Urban and Fischer Verlag
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier GmbH.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.etp.2013.02.005
• Title of Journal or Parent Work: Experimental and Toxicology Pathology
• Volume: 65
• Issue: 7-8
• Start Page: 1019
• End Page: 1024
• Keywords: Pathology; Epstein-Barr virus; Nonhuman primate; MONKEYS; Renal transplantation; SOLID-ORGAN TRANSPLANTATION; LYMPHOMA; Toxicology; EPSTEIN-BARR-VIRUS; MODEL; LYMPHOCRYPTOVIRUS INFECTION; Life Sciences & Biomedicine; Science & Technology; Post-transplant lymphoproliferative disorder
• Research Categories: Health Sciences, Rehabilitation and Therapy; Health Sciences, Immunology

Abstract

Human post-transplant lymphoproliferative disorder (PTLD) is an abnormal lymphoid proliferation that arises in 1-12% of transplant recipients as a consequence of prolonged immunosuppression and Epstein-Barr viral infection (EBV). Nonhuman primates, primarily rhesus macaques (Macaca mulatta), have been used extensively in research models of solid organ transplantation, as the nonhuman primate immune system closely resembles that of the human. Lymphocryptovirus of rhesus monkeys has been characterized and shown to be very similar to EBV in humans in regards to its cellular tropism, host immune response, and ability to stimulate B lymphocyte proliferation and lymphomagenesis. Thus, it appears that the NHP may be an appropriate animal model for EBV-associated lymphoma development in humans. The clinical management of post-transplant nonhuman primates that are receiving multiple immunosuppressive agents can be complicated by the risk of PTLD and other opportunistic infections. We report 3 cases of PTLD in rhesus macaques that illustrate this risk potential in the setting of potent immunosuppressive therapies for solid organ transplantation.