There has been much uncertainty regarding the identity of chronic active EBV infection and where it fits into the spectrum of EBV-associated disorders. Clinical observations and laboratory studies had defined it on the basis of 3 features: severe illness that begins as a primary EBV infection or that is associated with abnormal EBV antibody titers; histologic evidence of organ disease, such as hepatitis, pneumonitis, or bone marrow hypoplasia; and demonstration of EBV antigens or EBV DNA in tissue. Now, Kimura and colleagues (page280) add to our understanding of chronic active EBV infection by extensively evaluating 30 patients with the above features. Based on their data as well as on earlier smaller studies, they conclude that chronic active EBV infection is an illness characterized by EBV infection of T cells or NK cells. The disease may be distinguished into 2 subgroups based on the cell type infected, each group with somewhat different clinical manifestations and outcomes. Patients with the T-cell type had a shorter survival time than patients with the NK-cell type.
EBV usually infects B cells and, perhaps, epithelial cells, but not T cells or NK cells. Yet in patients with chronic active EBV infection, T or NK cells were the blood cells predominantly infected by the virus. These cells had probably undergone clonal expansion because virus recovered from the blood was generally monoclonal and blood cells often displayed various chromosomal aberrations. Thus, chronic active EBV infection might best be considered to be a lymphoproliferative disease. Indeed, many patients go on to develop EBV-positive lymphomas of T or NK phenotype. The question is why EBV infects these unusual cell targets. Here the authors provide some important negative information: the SAP/SH2D1A gene that is mutated in X-linked lymphoproliferative disease, an inherited disease resulting in unregulated growth of EBV-infected B cells, was not affected in these patients. The search for a genetic defect underlying chronic active EBV infection will certainly continue.
