Chronological changes in Epstein-Barr virus genome and subsets of peripheral mononuclear cells in a case of HLH


Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder characterized by high grade fever, heaptos-plenomegaly, lymphadenopathy and cytopenia in association with hypercytokinemia and macrophage activation. Epstein-Barr virus (EBV) is a common cause of HLH particularly in Asian countries. Although EBV usually infects B cells and causes infectious mononucleosis, it is detected predominantly in CD8+ T cells in EBV-associated HLH. In the present study we found the EBV genome in various lineages of the lymphoid cells including T, B, and natural killer cells in a 14-month-old boy with mild EBV-associated HLH. Furthermore, chronological changes in the copy number of EBV-DNA in each lineage are reported. Profound decrease in the number of peripheral natural killer cells at the early stage could be involved in the development of HLH.

Share and Cite:

Ukeba-Terashita, Y. , Saita, Y. , Ito, Y. , Kanegane, H. , Kimura, H. and Kobayashi, I. (2011) Chronological changes in Epstein-Barr virus genome and subsets of peripheral mononuclear cells in a case of HLH. Open Journal of Pediatrics, 1, 30-33. doi: 10.4236/ojped.2011.13008.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Henter, J-I., Horne, A.C., Aricó, M., et al. (2007) HLH- 2004: Diagnostic and therapeutic guidelines for hemo-phagocytic lymphohistiocytosis. Pediatric Blood & Can-cer, 48, 124-131. doi:10.1002/pbc.21039
[2] Ishii, E., Ohga, S., Imashuku, S., et al. (2007) Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. International Journal of Hematology, 86, 58-65. doi:10.1532/IJH97.07012
[3] Beutel, K., Gross-Wieltsch, U., Wiesel, T., Zur Stadt, U., Janka, G. and Wagner, H.-J. (2009) Infection of T lym-phocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children of non-Asian origin. Pediatric Blood & Cancer, 53, 184-190.
[4] Sonke, G.S., Ludwig, I., Van Oosten, H., et al. (2008) Poor utcomes of chronic active Epstein-Barr virus infec-tion and hemophagocytic lymphohistiocytosis in non-Ja- panese adult patients. Clinical Infectious Diseases, 47, 105-108. doi:10.1086/588790
[5] Kimura, H. (2006) Pathogenesis of chronic active Eps-tein-Barr virus infection: Is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Re-views in Medical Virology, 16, 251-261. doi:10.1002/rmv.505
[6] Kasahara, Y., Yachie, A., Takei, K., et al. (2001) Diffe-rential cellular target of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lym- phohistiocytosis and chronic active EBV infection. Blood, 98, 1882-1888. doi:10.1182/blood.V98.6.1882
[7] Kimura, H., Hoshino, Y., Kanegane, H., et al. (2001) Clinical and virological characteristics of chronic active Epstein-Barr virus infection. Blood, 98, 280-286. doi:10.1182/blood.V98.2.280
[8] Ayusawa, M., Sonobe, T., Uemura, S., et al., (2005) Revi-sion of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatrics International, 47, 232-234. doi:10.1111/j.1442-200x.2005.02033.x
[9] Kikuta, H., Sakiyama, Y., Matsumoto. S., et al. (1993) Detection of Epstein-Barr virus DNA in cardiac and aortic tissues from chronic, active Epstein-Barr virus infection associated with Kawasaki disease-like coronary artery aneurysms. Journal of Pediatrics, 123, 90-92. doi:10.1016/S0022-3476(05)81546-X
[10] Binstadt, B.A., Levine, J.C., Nigrovic, P.A., et al. (2005) Coronary artery dilation among patients presenting with systemic-onset juvenile idiopathic arthritis. Pediatrics, 116, e89-e93. doi:10.1542/peds.2004-2190
[11] Kogawa, K., Lee, S.M., Vilanueva, J., et al. (2002) Per-forin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members. Blood, 99, 61-66. doi:10.1182/blood.V99.1.61
[12] Chuang, H.-C., Hsie, W.-C., Wang, H.-C., et al. (2005) Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome. Blood, 106, 3090-3096. doi:10.1182/blood-2005-04-1406
[13] Williams, H., McAulay, K., Macsween, K.F., et al. (2005) The immune response to primary EBV infection: A role for natural killer cells. British Journal of Haematology, 129, 266-274. doi:10.1111/j.1365-2141.2005.05452.x
[14] Kimura, H., Morita, M., Yabuta, Y., et al. (1999) Quan-titative analysis of Epstein-Barr virus load by using real-time PCR assay. J Clin Microbiol., 37, 132.
[15] Kimura, H., Hoshino, Y., Hara, S., et al. (2002) Viral load in Epstein-Barr virus-associated hemophagocytic syn-drome. Microbiology and Immunology, 46, 579-582.
[16] Trempat, P., Tabiasco, J., Andre, P., et al. (2002) Evidence for early infection of nonneoplastic natural killer cells by Epstein-Barr virus. Journal of Virology, 76, 11139-11142. doi:10.1128/JVI.76.21.11139-11142.2002
[17] Isobe, Y., Sugimoto, K., Yang, L, et al. (2004) Epstein- Barr virus infection of human natural killer cell lines and peripheral blood natural killer cells. Cancer Research, 64, 2167-2174.
[18] Imashuku, S., Obayashi, M., Hosoi, G., et al. (2000) Splenectomy in haemophagocytosis: Report of histopa-thological changes with CD19; B-cell depletion and the-rapeutic results. British Journal of Haematology, 108, 505-510. doi:10.1046/j.1365-2141.2000.01904.x
[19] Nimmerjahn, F. and Ravetch, J.V. (2008) Anti-inflam- matory actions of intravenous immunoglobulin. Annual Review of Immunology, 26, 513-533. doi:10.1146/annurev.immunol.26.021607.090232

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.