Mutations in latent membrane protein 1 of Epstein-Barr virus are associated with increased risk of posttransplant lymphoproliferative disorder in children.
Am J Transplant
; 23(5): 611-618, 2023 05.
Article
en En
| MEDLINE
| ID: mdl-36796762
ABSTRACT
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 (12 nested casecontrol), 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones por Virus de Epstein-Barr
/
Trastornos Linfoproliferativos
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2023
Tipo del documento:
Article