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

Abstract

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.

Systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood: Report of a case with review of the literature

“…The majority of previous studies have reported single cases; however, the study by Quintanilla-Martinez et al described the clinicopathological features of 5 cases of this disease (2). In this study, we reviewed the clinicopatho- logical features of 17 cases with systemic EBV-positive T-cell LPD of childhood following acute EBV infection, including the present case (Table I) (2,(4)(5)(6)(7)(8)(9)(10)(11)(12). We revealed that clonal systemic proliferation of EBV-infected T-cells that appear morphologically innocuous with an activated cytotoxic phenotype expressing CD8 and/or CD4 is central to the disease.…”

Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations

“…The majority of published data have confirmed that CD3 + T cells, most often the CD8 + subset, both in tissue biopsies [21,49,51,52,55-57] and circulating lymphocytes [26,58], are the dominant infected population in EBV-HLH. However, unequivocal infection of NK cells has also been observed, and may even be the dominant infected cell type in some patients [59].…”

Treatment of Epstein‐Barr virus‐associated hemophagocytic lymphohistiocytosis (EBV‐HLH) in young adults: A report from the HLH studyl center

“…There are reports that plasmapheresis [12,17,18], intravenous immunoglobulin (IVIG) [19,20], cyclosporin A (CSA) [21,22], etoposide [3,7,12], and a combination of IVIG and etoposide [23] have been effective. However, there is no consensus in the literature, which of these treatments is optimal [24].…”

“…EBV-HLH occurs in both children [7,12] and young adults (defined as older than 15 years of age) [1,[3][4][5][6][8][9][10][11][27][28][29]. It is not clear whether the etoposide therapy would also be effective in young adults.…”

“…Epstein-Barr virus (EBV)-associated hemophagocytic syndrome has been reported to occur in association with infectious mononucleosis [1,2], chronic active EBV infection [3,4], EBV-positive T-cell lymphoproliferative disorder or lymphoma [5][6][7], and natural killer (NK)-cell granular lymphocyte proliferative disorders-or leukemiaassociated hemophagocytic syndrome (EBV-NK-LAHS) [8][9][10][11]. The syndrome is also known as EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) [12], the term used in this study.…”