EBV deletions as biomarkers of response to treatment of Chronic Active Epstein Barr Virus. Chronic active EBV cases

Chronic active Epstein Barr Virus (CAEBV) is a rare and severe condition occurring in previously healthy individuals associated with persistent EBV viraemia, fever, lymphadenopathy and hepatosplenomegaly. Specific deletions in the EBV genome have been found in CAEBV and certain lymphomas. However, it is unclear how stable these deletions are, whether they are present in different sites and how they evolve in response to treatment. We sequenced fifteen longitudinal blood samples from three CAEBV patients, comparing the results with 13 saliva samples from CAEBV patients and sequences from benign (both primary infection and reactivation) and malignant EBV-related conditions. We observed large EBV deletions in blood, some of which are predicted to disrupt viral replication, but not saliva from patients with CAEBV. Deletions were stable over time but were lost following successful peripheral blood stem cell transplants (PBSCT) or in one case, treatment with rituximab. Our results are consistent with the likelihood that certain deletions occurring in virus from patients with CAEBV are associated with the evolution and persistence of haematological clones. We propose that the loss of EBV deletions following successful treatment should be investigated as a potential biomarker to aid management of CAEBV.

慢性活动性EB病毒感染（Chronic active Epstein-Barr Virus, CAEBV）是一种罕见且危重的疾病，好发于既往健康个体，与持续性EB病毒血症、发热、淋巴结病及肝脾肿大密切相关。研究已在CAEBV及部分淋巴瘤中检出EB病毒基因组的特异性缺失。然而，目前尚不明确这些缺失的稳定性、是否存在于不同组织部位，以及其在治疗干预下的演化规律。本研究对3名CAEBV患者的15份纵向血液样本进行了测序，并将测序结果与13份CAEBV患者的唾液样本，以及良性EB病毒相关疾病（涵盖原发性感染与病毒再激活）、恶性EB病毒相关疾病的测序数据进行了对比分析。研究团队在患者血液样本中观察到大片段EB病毒缺失，部分缺失经预测可破坏病毒复制过程，但此类缺失未在CAEBV患者的唾液样本中检出。上述缺失随时间推移保持稳定，但在成功接受外周血干细胞移植（PBSCT）后，或在1例患者接受利妥昔单抗治疗后消失。本研究结果与下述可能性相符：CAEBV患者体内病毒发生的部分缺失，与造血克隆的演化及持续存在密切相关。我们建议将成功治疗后EB病毒缺失的消失作为潜在生物标志物，用于辅助CAEBV的临床管理。