Characterisation of pathogenetic mechanisms of Epstein-Barr virus-associated T and natural killer cell lymphoproliferative diseases in children

Professor Chiang, Alan Kwok Shing   (Principal Investigator (PI))

Professor Chen Zhiwei   (Co-Investigator)

36

2021-10-01

1000000

Characterisation of pathogenetic mechanisms of Epstein-Barr virus-associated T and natural killer cell lymphoproliferative diseases in children

Chronic active EBV infection (CAEBV), EBV-associated T/NK LPDs, Epstein-Barr virus (EBV), Hemophagocytic lymphohistiocytosis (HLH), Infectious mononucleosis (IM), Single-cell RNA sequencing

Others - Medicine, Dentistry and Health

20190432

Health and Medical Research Fund - Full Grant

2020

On-going

Background: Primary Epstein-Barr virus (EBV) infection is associated with T and natural killer cell lymphoproliferative diseases (EBV-T/NK LPDs) in immunocompetent children. The severity and progression of the diseases vary among individuals, which may correlate to the different cellular targets of EBV and pathogenic pathways involved. Our preliminary findings suggested that T and NK cell functions are impaired at diagnosis whilst their function can be restored if the diseases can enter remission. The ectopic EBV infection in T or NK cells may cause reversible impairment of T and NK cell functions and play a role in the pathogenesis of EBV-T/NK LPDs. Objectives: We aim to determine the EBV-infected cell types in the peripheral blood mononuclear cells (PBMCs) of EBV-T/NK LPDs patients. Longitudinal phenotypic and functional analyses of EBV-specific T and NK cells will be examined. We will also conduct dual-omics analyses on whole transcriptome and proteomics on PBMCs to elucidate the pathogenic mechanisms of EBV-T/NK LPDs. Methods: Phenotypic profile of EBV-infected cell types will be determined through Primeflow RNA assay. Phenotypic and functional assays including the measurement of cytokine production and degranulation in T and NK cell subsets will be performed. The comprehensive transcriptomic and proteomic profile of EBV-T/NK LPDs patients will be conducted through BD Rhapsody system. Outcomes: Distinct pathogenic pathways correlating to defective control of EBV in patients with EBV-T/NK LPDs will be elucidated. Potential application: The pathogenic pathways identified may lead to rational development of more specific treatment strategies for EBV-T/NK LPDs.