Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infection

BackgroundThe prospective application of plasma Epstein-Barr virus (EBV) DNA load as a noninvasive measure of intestinal EBV infection remains unexplored. This study aims to identify ideal threshold levels for plasma EBV DNA loads in the diagnosis and outcome prediction of intestinal EBV infection,...

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Main Authors: Chunxiang Ma, Mingshan Jiang, Jiaxin Li, Zhen Zeng, Yushan Wu, Rui Cheng, Hao Lin, Jiangmei Pang, Fang Yin, Yongbin Jia, Lili Li, Hu Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2024.1526633/full
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author Chunxiang Ma
Chunxiang Ma
Chunxiang Ma
Mingshan Jiang
Mingshan Jiang
Mingshan Jiang
Jiaxin Li
Jiaxin Li
Jiaxin Li
Zhen Zeng
Zhen Zeng
Zhen Zeng
Yushan Wu
Yushan Wu
Yushan Wu
Rui Cheng
Rui Cheng
Rui Cheng
Hao Lin
Hao Lin
Hao Lin
Jiangmei Pang
Jiangmei Pang
Jiangmei Pang
Fang Yin
Fang Yin
Fang Yin
Yongbin Jia
Yongbin Jia
Yongbin Jia
Lili Li
Lili Li
Lili Li
Hu Zhang
Hu Zhang
Hu Zhang
author_facet Chunxiang Ma
Chunxiang Ma
Chunxiang Ma
Mingshan Jiang
Mingshan Jiang
Mingshan Jiang
Jiaxin Li
Jiaxin Li
Jiaxin Li
Zhen Zeng
Zhen Zeng
Zhen Zeng
Yushan Wu
Yushan Wu
Yushan Wu
Rui Cheng
Rui Cheng
Rui Cheng
Hao Lin
Hao Lin
Hao Lin
Jiangmei Pang
Jiangmei Pang
Jiangmei Pang
Fang Yin
Fang Yin
Fang Yin
Yongbin Jia
Yongbin Jia
Yongbin Jia
Lili Li
Lili Li
Lili Li
Hu Zhang
Hu Zhang
Hu Zhang
author_sort Chunxiang Ma
collection DOAJ
description BackgroundThe prospective application of plasma Epstein-Barr virus (EBV) DNA load as a noninvasive measure of intestinal EBV infection remains unexplored. This study aims to identify ideal threshold levels for plasma EBV DNA loads in the diagnosis and outcome prediction of intestinal EBV infection, particularly in cases of primary intestinal lymphoproliferative diseases and inflammatory bowel disease (IBD).MethodsReceiver operating characteristic (ROC) curves were examined to determine suitable thresholds for plasma EBV DNA load in diagnosing intestinal EBV infection and predicting its prognosis.Results108 patients were retrospectively assigned to the test group, while 56 patients were included in the validation group. Plasma EBV DNA loads were significantly higher in the intestinal EBV infection group compared to the non-intestinal EBV infection group (Median: 2.02 × 102 copies/mL, interquartile range [IQR]: 5.49 × 101-6.34×103 copies/mL versus 4.2×101 copies/mL, IQR: 1.07 ×101-6.08×101 copies/mL; P < 0.0001). Plasma EBV DNA levels at 9.21×101 and 6.77×101 copies/mL proved beneficial for the identification and prognostication in intestinal EBV infection, respectively. Values of 0.82 and 0.71 were yielded by the area under the ROC curve (AUC) in the test cohort, corresponding to sensitivities of 84.38% (95% confidence interval [95%CI]: 68.25%-93.14%) and 87.5% (95%CI: 69%-95.66%), specificities of 83.33% (95%CI: 64.15%-93.32%) and 68.09% (95%CI: 53.83%-79.6%), positive predictive values (PPV) of 87.1% (95%CI: 71.15%-94.87%) and 58.33% (95%CI: 42.2%-72.86%), and positive likelihood ratios (LR+) of 5.06 and 2.74 in the validation cohort, respectively. Furthermore, a plasma EBV DNA load of 5.4×102 copies/mL helped differentiate IBD with intestinal EBV infection from primary intestinal EBV-positive lymphoproliferative disorders (PIEBV+LPDs), achieving an AUC of 0.85 within the test cohort, as well as 85% sensitivity (95%CI: 63.96%-94.76%), 91.67% specificity (95%CI: 64.61%-99.57%), 94.44% PPV (95%CI: 74.24%-99.72%), and an LR+ of 10.2 in the validation cohort.ConclusionsPlasma EBV DNA load demonstrates notable potential in distinguishing between different patient cohorts with intestinal EBV infection, although its sensitivity requires further optimization for clinical application.
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spelling doaj-art-f7d084f000a34d0da2a1c9189c33d5d42025-01-07T06:46:22ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.15266331526633Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infectionChunxiang Ma0Chunxiang Ma1Chunxiang Ma2Mingshan Jiang3Mingshan Jiang4Mingshan Jiang5Jiaxin Li6Jiaxin Li7Jiaxin Li8Zhen Zeng9Zhen Zeng10Zhen Zeng11Yushan Wu12Yushan Wu13Yushan Wu14Rui Cheng15Rui Cheng16Rui Cheng17Hao Lin18Hao Lin19Hao Lin20Jiangmei Pang21Jiangmei Pang22Jiangmei Pang23Fang Yin24Fang Yin25Fang Yin26Yongbin Jia27Yongbin Jia28Yongbin Jia29Lili Li30Lili Li31Lili Li32Hu Zhang33Hu Zhang34Hu Zhang35Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, ChinaLab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaBackgroundThe prospective application of plasma Epstein-Barr virus (EBV) DNA load as a noninvasive measure of intestinal EBV infection remains unexplored. This study aims to identify ideal threshold levels for plasma EBV DNA loads in the diagnosis and outcome prediction of intestinal EBV infection, particularly in cases of primary intestinal lymphoproliferative diseases and inflammatory bowel disease (IBD).MethodsReceiver operating characteristic (ROC) curves were examined to determine suitable thresholds for plasma EBV DNA load in diagnosing intestinal EBV infection and predicting its prognosis.Results108 patients were retrospectively assigned to the test group, while 56 patients were included in the validation group. Plasma EBV DNA loads were significantly higher in the intestinal EBV infection group compared to the non-intestinal EBV infection group (Median: 2.02 × 102 copies/mL, interquartile range [IQR]: 5.49 × 101-6.34×103 copies/mL versus 4.2×101 copies/mL, IQR: 1.07 ×101-6.08×101 copies/mL; P < 0.0001). Plasma EBV DNA levels at 9.21×101 and 6.77×101 copies/mL proved beneficial for the identification and prognostication in intestinal EBV infection, respectively. Values of 0.82 and 0.71 were yielded by the area under the ROC curve (AUC) in the test cohort, corresponding to sensitivities of 84.38% (95% confidence interval [95%CI]: 68.25%-93.14%) and 87.5% (95%CI: 69%-95.66%), specificities of 83.33% (95%CI: 64.15%-93.32%) and 68.09% (95%CI: 53.83%-79.6%), positive predictive values (PPV) of 87.1% (95%CI: 71.15%-94.87%) and 58.33% (95%CI: 42.2%-72.86%), and positive likelihood ratios (LR+) of 5.06 and 2.74 in the validation cohort, respectively. Furthermore, a plasma EBV DNA load of 5.4×102 copies/mL helped differentiate IBD with intestinal EBV infection from primary intestinal EBV-positive lymphoproliferative disorders (PIEBV+LPDs), achieving an AUC of 0.85 within the test cohort, as well as 85% sensitivity (95%CI: 63.96%-94.76%), 91.67% specificity (95%CI: 64.61%-99.57%), 94.44% PPV (95%CI: 74.24%-99.72%), and an LR+ of 10.2 in the validation cohort.ConclusionsPlasma EBV DNA load demonstrates notable potential in distinguishing between different patient cohorts with intestinal EBV infection, although its sensitivity requires further optimization for clinical application.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1526633/fullEpstein-Barr virus DNA loaddiagnosisprognosisinflammatory bowel diseasesprimary intestinal lymphoproliferative diseasesintestinal Epstein-Barr Virus infection
spellingShingle Chunxiang Ma
Chunxiang Ma
Chunxiang Ma
Mingshan Jiang
Mingshan Jiang
Mingshan Jiang
Jiaxin Li
Jiaxin Li
Jiaxin Li
Zhen Zeng
Zhen Zeng
Zhen Zeng
Yushan Wu
Yushan Wu
Yushan Wu
Rui Cheng
Rui Cheng
Rui Cheng
Hao Lin
Hao Lin
Hao Lin
Jiangmei Pang
Jiangmei Pang
Jiangmei Pang
Fang Yin
Fang Yin
Fang Yin
Yongbin Jia
Yongbin Jia
Yongbin Jia
Lili Li
Lili Li
Lili Li
Hu Zhang
Hu Zhang
Hu Zhang
Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infection
Frontiers in Cellular and Infection Microbiology
Epstein-Barr virus DNA load
diagnosis
prognosis
inflammatory bowel diseases
primary intestinal lymphoproliferative diseases
intestinal Epstein-Barr Virus infection
title Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infection
title_full Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infection
title_fullStr Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infection
title_full_unstemmed Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infection
title_short Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infection
title_sort plasma epstein barr virus dna load for diagnostic and prognostic assessment in intestinal epstein barr virus infection
topic Epstein-Barr virus DNA load
diagnosis
prognosis
inflammatory bowel diseases
primary intestinal lymphoproliferative diseases
intestinal Epstein-Barr Virus infection
url https://www.frontiersin.org/articles/10.3389/fcimb.2024.1526633/full
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