Surveillance and Tracking the Outcomes of Chronic Latent EBV Infection

Study to Surveil and Track the Outcomes of Chronic Latent EBV Infection Based on Healthy Volunteers Undergoing Routine Inspection

Immunocompetent subjects with high load of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood will be enrolled and prospectively followed up to track the natural histories of the chronic high load of EBV virus. The primary goal of this study is to explore the association of peripheral high load of EBV with the hematological malignancies, and second goal is to investigate the genetic mechanisms of immune escape and tumorigenesis of chronic EBV infection.

Epstein-Barr virus (EBV) is an oncogenic virus implicated in the pathogenesis of a variety of human hematological malignancies such as lymphomas, hemophagocytic lymphohistiocytosis and chronic active EBV disease. While chronic latent EBV infection（especially carriers with persistent high load of EBV-DNA copy number）is the gray zone between the primary infection and the hematological malignancies, which is rarely concerned. Previous work has prompted the heterogeneities of EBV infection, such as racial heterogeneity, viral load heterogeneity and heterogeneity of infected target cells. It is of great significance to prospectively track the transforming process and elucidate the association of chronic EBV infection and hemophagocytic lymphohistiocytosis. Healthy subjects who was found to have high EBV-DNA load （>1×103 copies/ml）in peripheral blood during the physical examination were enrolled and followed up by telephone or face-to-face interview periodically. The primary outcome is hematological malignancies including Burkitt lymphoma, EBV+ B-cell lymphoproliferative diseases, extranodal NK/T-cell lymphoma of nasal type (ENKL), aggressive NK-cell leukemia (ANKL), classic Hodgkin lymphoma,EBV-associated hemophagocytic lymphohistiocytosis and Chronic active Epstein-Barr virus infection (CAEBV). The Exploratory purpose of this study is to investigate of genetic mechanisms of immune escape and tumorigenesis of EBV infection. Subgroup analysis will performed in subjects with mild high load (>1×103 copies/ml and <1×104 copies/ml) and severe high load (>1×104 copies/ml) of EBV-DNA copies.

Inclusion Criteria:

1. immunocompetent subjects who was found to have high EBV-DNA load （>1×103 copies/ml）in peripheral blood during the physical examination
2. Willing to be followed up by telephone or face-to-face interview

Exclusion Criteria:

1. Subjects with defined immunodeficiency
2. Subjects who have taken or are going to take immunosuppressive drugs.
3. Subjects Diagnosed a validated hematopathy
4. Subjects diagnosis as precancerous lesion or malignant tumor and the life expectancy is less than 1 year.
5. psychological illness which does not allow subjects to understand the study and participate following his own free will
6. Pregnant woman
7. no written informed consent