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
em 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por Vírus Epstein-Barr
/
Transtornos Linfoproliferativos
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Child
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Humans
Idioma:
En
Revista:
Am J Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2023
Tipo de documento:
Article