Epstein-Barr virus genes in patients with acute, chronic and recurrent hemophagocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH), a rare disorder primarily of childhood, typically presents with fever, hepatosplenomegaly, lymphadenopathy, and sometimes vague or dramatic central nervous system (CNS) dysfunction. Leading triggering agents in HLH are viruses of the herpes group, especially Epstein-Barrvirus (EBV). In addition to high concentrations of cytokines, states of EBV-infected T/NK cells appear to play a role in the development of EBV-associated HLH. Since EBV establishes a life-long persistent infection in more than 90% of the population worldwide, it is necessary to know how EBV may be related to HLH. We investiged 9 patients with histories of acute, chronic, and recurrent HLH, the relationships between the valuable disease marker of HLH, the concentration of soluble Cluster of Differentiation antigen (sCD25) in their plasma from different time points, and the EBV target genes, Epstein-Barrvirus nuclear antigen 1 (EBNA1), EBNA2, EBNA3C, EBV lytic activation 1 (BZLF1), BMLF1, Nonglycosylated membrane protein 1 (BNRF1) and latent membrane protein 1 (LMP1) of paired samples from these 9 patients. Our results demonstrated that BZLF1 and EBNA3c genes were present in active HLH patients, which are found in whole blood, and isolated cells concomitantly with high concentration of plasma sCD25. In conclusion: BZLF1 and EBNA3c genes were associated with active HLH. Single cell PCR appears to be a prominent set up be applied for the contributuion of EBV in HLH as well as other diseases including tumor manifestation.