Monoclonal proliferation of Epstein-Barr virus-infected T-cells in a patient with virus-associated haemophagocytic syndrome.

Virus-associated haemophagocytic syndrome (VAHS) is a non-neoplastic, generalized histiocytic proliferation disorder showing marked haemophagocytosis associated with systemic viral infection. We describe the case of a 1-year-old girl with Epstein-Barr virus (EBV)-related VAHS, in whom Southern blot analysis showed monoclonal proliferation of bone marrow cells with the EBV genome; detected with the Xho-1 fragment of the latent infection membrane protein genome. EBV serology showed anti-Epstein-Barr virus nuclear associated antigen (EBNA), anti-viral capsid antigen (VCA)-IgG, anti-VCA-IgA elevation and positive EBNA of Sheep red blood cells (SRBC)-rosette-forming bone marrow cells in the late period of her clinical course, indicative of EBV infection. DNA analysis of her bone marrow cells showed monoclonal rearrangement of the T-cell receptor-beta and -gamma chain genes but not of the immunoglobulin heavy chain genes. Those results suggest that EBV may infect T-cells, after which the cells proliferate monoclonally. Repeated administration of epipodophyllotoxin VP-16-213 induced remission, but adrenocortical steroid, vincristine, and cyclophosphamide had no effect on the patient's condition. Ours is a first case report of VAHS showing monoclonal proliferation of EBV-infected T-cells.