High levels of Tfh/B-cell gene expression suggests poor prognosis in systemic chronic active Epstein-Barr virus disease

Abstract Systemic chronic active Epstein-Barr virus (CAEBV) disease is presumed to be caused by abnormal immunity toward EBV; however, its biological mechanism remains unknown. We investigated invasive immune-cell gene and EBV gene expressions in systemic CAEBV disease by comparing EBV-positive T-/NK-cell lymphomas (extranodal NK-/T-cell lymphoma [ENKTL] and EBV-positive nodal T- and NK-cell lymphoma [EBV-N-TNKL]). Gene expression profiling revealed a correlation between the expression levels of follicular helper T (Tfh)-cell and B-cell genes in systemic CAEBV disease. When we divided the patients into two groups according to the number of B-cells by immunohistochemistry, the B-cell high-count group showed a poorer prognosis than the low-count group. Additionally, the high-count group had higher EBV gene levels and EBV-positive B-cell counts than the low-count group. These results suggest that the clinical symptoms may be explained by the expansion of EBV-positive B-cells, resulting in a poor prognosis. Differential gene expression analysis revealed that systemic CAEBV disease exhibited more diverse gene expression levels than ENKTL and EBV-N-TNKL. The most significant variable genes were identified as novel distinguishing markers for systemic CAEBV disease. In conclusion, Tfh-cell and B-cell gene expression and diverse gene expression levels may correlate with unique clinical symptoms and prognosis in systemic CAEBV disease.