Mutations in latent membrane protein 1 of Epstein-Barr virus are associated with increased risk of posttransplant lymphoproliferative disorder in children.

Autor:	Martinez OM; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA; Stanford Immunology, Stanford University School of Medicine, Palo Alto, California, USA. Electronic address: omm@stanford.edu., Krams SM; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA; Stanford Immunology, Stanford University School of Medicine, Palo Alto, California, USA., Robien MA; National Institute of Allergy and Infectious Disease, Rockville, Maryland, USA., Lapasaran MG; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA., Arvedson MP; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA., Reitsma A; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA., Balachandran Y; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA., Harris-Arnold A; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA; Stanford Immunology, Stanford University School of Medicine, Palo Alto, California, USA., Weinberg K; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA., Boyd SD; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Armstrong B; Rho, Durham, North Carolina, USA., Trickey A; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA., Twist CJ; Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA., Gratzinger D; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Tan B; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Brown M; National Institute of Allergy and Infectious Disease, Rockville, Maryland, USA., Chin C; Department of Pediatrics and Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio, USA., Desai DM; University of Texas Southwestern Medical Center, Dallas, Texas, USA., Fishbein TM; Departments of Surgery and Pediatrics, MedStar Georgetown University Hospital, Georgetown, Washington, DC, USA., Mazariegos GV; University of Pittsburgh Medical Center, Children's Hospital Pittsburgh, Pittsburgh, Pennsylvania, USA., Tekin A; Miller School of Medicine, University of Medicine, Florida, USA., Venick RS; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA., Bernstein D; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA., Esquivel CO; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA.
Jazyk:	angličtina
Zdroj:	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2023 May; Vol. 23 (5), pp. 611-618. Date of Electronic Publication: 2023 Feb 15.
DOI:	10.1016/j.ajt.2023.02.014
Abstrakt:	Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) results in significant morbidity and mortality in pediatric transplant recipients. Identifying individuals at an increased risk of EBV-positive PTLD could influence clinical management of immunosuppression and other therapies, improving posttransplant outcomes. A 7-center prospective, observational clinical trial of 872 pediatric transplant recipients evaluated the presence of mutations at positions 212 and 366 of EBV latent membrane protein 1 (LMP1) as an indicator of risk of EBV-positive PTLD (clinical trials: NCT02182986). DNA was isolated from peripheral blood of EBV-positive PTLD case patients and matched controls (1:2 nested case:control), and the cytoplasmic tail of LMP1 was sequenced. Thirty-four participants reached the primary endpoint of biopsy-proven EBV-positive PTLD. DNA was sequenced from 32 PTLD case patients and 62 matched controls. Both LMP1 mutations were present in 31 of 32 PTLD cases (96.9%) and in 45 of 62 matched controls (72.6%) (P = .005; OR = 11.7; 95% confidence interval, 1.5, 92.6). The presence of both G212S and S366T carries a nearly 12-fold increased risk of development of EBV-positive PTLD. Conversely, transplant recipients without both LMP1 mutations carry a very low risk of PTLD. Analysis of mutations at positions 212 and 366 of LMP1 can be informative in stratifying patients for risk of EBV-positive PTLD. (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. All rights reserved.)
Databáze:	MEDLINE
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