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Lytic infection of Epstein-Barr virus (EBV) in hemophagocytic syndrome associated with EBV-induced lymphoproliferative disorder

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Abstract

This report describes lytic infection with Epstein-Barr virus (EBV) in three cases of hemophagocytic syndrome (HPS) presumably associated with EBV-induced lymphoproliferative disorder. All cases were previously healthy females with ages ranging from 52 to 87 years who showed a fulminant clinical course with accompanying fever, liver dysfunction, and disseminated intravascular coagulation. Cases 1 and 2 showed proliferation of atypical T lymphocytes, and case 3 showed proliferation of atypical B lymphocytes. Hemophagocytic histiocytes were observed in the bone marrow, lymph nodes, spleen, and liver. Atypical lymphocytes in all cases showed a positive reaction for both EBV-encoded small RNA (EBER) indicating latent infection with EBV and immediate early mRNAs of the Bam HI fragment of lower stranded frame (BHLF), indicating lytic infection by in situ hybridization. Interestingly, BHLF-positive cells were predominant in all cases. It is possible that reactivation of EBV infection may be involved in triggering the induction of cytokines and abnormal activation of histiocytes.

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References

  1. Arcenas R, Widen RH (2002) Epstein-Barr virus reactivation after superinfection of the BJAB-B1 and P3HR-1 cell lines with cytomegalovirus. BMC Microbiol 23:20.

    Article  Google Scholar 

  2. Cui S, Maruoka Y, Ando T, Kobayashi M, Ogiuchi H (2001) Role of Epstein-Barr virus infection in oral diseases. J Tokyo Wom Med Univ 71:7-15

    Google Scholar 

  3. Epstein MA, Achong BG, Barr YM (1964) Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1:702–703

    Google Scholar 

  4. Gaillard F, Mechinaud-Lacroix F, Papin S, Moreau A, Mollat C, Fiche M, Peitler S, de Faucal PJ, Rousselet M-C, Praloran V, Harousseau J-L (1992) Primary Epstein-Barr virus infection with clonal T-cell lymphoproliferation. Am J Clin Pathol 98:324–333

    CAS  PubMed  Google Scholar 

  5. Hopwood PA, Brooks L, Parratt R, Hunt BJ, Maria B, Alero TJ, Magdi Y, Crawford DH (2002) Persistent Epstein-Barr virus infection: unrestricted latent and lytic viral gene expression in healthy immunosuppressed transplant recipients. Transplantation 74:194–202

    CAS  PubMed  Google Scholar 

  6. Hsu CH, Hergenhahn M, Chuang SE, Yeh PY, Wu TC, Gao M, Cheng AL (2002) Induction of Epstein-Barr virus (EBV) reactivation in Raji cells by doxorubicin and cisplatin. Anticancer Res 22:4065–4071

    CAS  PubMed  Google Scholar 

  7. Imashuku S (1997) Differential diagnosis of hemophagocytic syndrome: underlying disorders and selection of the most effective treatment. Int J Hematol 66:135–151

    CAS  PubMed  Google Scholar 

  8. Jaffe ES, Chan JKC, Su I-J, Frizzera G, Mori S, Feller AC, Ho FCS (1996) Report of the workshop on nasal and related extranodal angiocentric T/Natural killer cell lymphomas. Am J Surg Pathol 20:103–111

    CAS  PubMed  Google Scholar 

  9. Kim IS, Park CK, Kim H, Lee YY, Ahn MJ, Lee WS (1997) Epstein-Barr virus associated hemophagocytic syndrome. A case report. J Korean Med Sci 12:447–451

    CAS  PubMed  Google Scholar 

  10. Larcher C, McQuain C, Berger C, Mitterer M, Quesenberry PJ, Huemer HP, Knecht H (1997) Epstein-Barr virus-associated persistent polyclonal B-cell lymphocytosis with a distinct 69-base pair deletion in the LMP1 oncogene. Ann Hematol 74:23–28

    Article  CAS  PubMed  Google Scholar 

  11. Mitterer M, Pescosta N, Fend F, Larcher C, Prang N, Schwarzmann F, Coser P, Huemer HP (1995) Chronic active Epstein-Barr virus disease in a case of persistent polyclonal lymphocytosis. Br J Haematol 90:526–531

    CAS  PubMed  Google Scholar 

  12. Mueller N, Evans A, Harris NL, Comstock GW, Jellum E, Magnus K, Orentreich N, Polk F, Vogelman J (1989) Hodgkin’s disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med 320:689–695

    CAS  PubMed  Google Scholar 

  13. Nazaruk RA, Rochford R, Hobbs MV, Cannon MJ (1998) Functional diversity of the CD8+ T-cell response to Epstein-Barr virus (EBV): implication for the pathogenesis of EBV-associated lymphoproliferative disorders. Blood 91:3875–3883

    CAS  PubMed  Google Scholar 

  14. Ohga S, Nomura A, Takada H, Ihara K, Kawakami K, Yanai F, Takahata Y, Tanaka T, Kasuga N, Hara T (2001) Epstein-Barr virus (EBV) load and cytokine gene expression in activated T cells of chronic active EBV infection. J Infect Dis 183:1-7

    Article  CAS  PubMed  Google Scholar 

  15. Okano M, Gross TG (1996) Epstein-Barr virus-associated hemophagocytic syndrome and fatal infectious mononucleosis. Am J Hematol 53:111–115

    Article  CAS  PubMed  Google Scholar 

  16. Otteman LA, Greipp PR, Ruiz-Argüelles GJ, Banks PM, Li C-Y, Katzmann JA (1985) Infectious mononucleosis mimicking a B cell immunoblastic lymphoma associated with an abnormality in regulatory T cells Am J Med 78:885–890

    CAS  Google Scholar 

  17. Oyama T, Ichimura K, Suzuki R, Suzumiya J, Ohshima K, Yatabe Y, Yokoi T, Kojima M, Kamiya Y, Taji H, Kagami Y, Ogura M, Saito H, Morishima Y, Nakamura S (2003) Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol 27:16–26

    Article  PubMed  Google Scholar 

  18. Quitanilla-Martinez L, Kumar S, Fend F, Reyes E, Teruya-Feldstein J, Kingma DW, Sorbara L, Raffeld M, Straus SE, Jaffe ES (2000) Fulminant EBV+ T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome. Blood 96:443–451

    CAS  PubMed  Google Scholar 

  19. Ryon JJ, Hayward SD, MacMahon EM, Mann RB, Ling Y, Charache P, Phelan JA, Miller G, Ambinder RF (1993) In situ detection of lytic Epstein-Barr virus infection: expression of the Notl early gene and viral interleukin-10 late gene in clinical specimens. J Infect Dis 168:345–351

    CAS  PubMed  Google Scholar 

  20. Shimakage M, Sasagawa T, Kawahara K, Yutsudo M, Kusuoka H, Kozuka T (2001) Expression of Epstein-Barr virus in cutaneous T-cell lymphoma including mycosis fungoides. Int J Cancer 92:226–231

    Article  CAS  PubMed  Google Scholar 

  21. Simon M, Bartram CR, Friedrich W, Arnold R, Schmeiser T, Hampl W, Müller-Hermelink HK, Heymer B (1991) Fatal B-cell lymphoproliferative syndrome in allogeneic marrow graft recipients. A clinical, immunobiological and pathological study. Virchows Arch B Cell Pathol 60:307–319

    CAS  Google Scholar 

  22. Steven NM, Annels NE, Kumar A, Leese AM, Kurilla MG, Rickinson AB (1997) Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response. J Exp Med 185:1605–1617

    Article  CAS  PubMed  Google Scholar 

  23. Takahashi N, Chubachi A, Kume M, Hatano Y, Komatsuda A, Kawabata Y, Yanagiya N, Ichikawa Y, Miura AB, Miura I (2001) A clinical analysis of 52 adult patients with hemophagocytic syndrome: the prognostic significance of the underlying diseases. Int J Hematol 74:209–213

    CAS  PubMed  Google Scholar 

  24. Yufu Y, Kimura M, Kawano R, Noguchi Y, Takatsuki H, Uike N, Ohshima K (2000) Epstein-Barr virus-associated T cell lymphoproliferative disorder following autologous blood stem cell transplantation for relapsed Hodgkin’s disease. Bone Marrow Transplant 26:1339–1341

    Google Scholar 

  25. Weiss LM, Movahed L, Warnke RA, Sklar J (1989) Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin’s disease. N Engl J Med 320:502–506

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors wish to thank F. Muramatsu for his excellent technical assistance.

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Authors and Affiliations

  1. Department of Pathology and Surgical Pathology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan

    T. Yamamoto & M. Kobayashi

  2. Clinical Laboratory, Sumitomo Besshi Hospital, 3-1 Oji-cho Niihama-shi, 792-8543, Ehime, Japan

    A. Shirakawa

  3. Department of Pathology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan

    M. Kawaguchi

  4. Department of Surgical Pathology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan

    A. Masuda & T. Nishikawa

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  1. T. Yamamoto
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  2. A. Shirakawa
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  3. M. Kawaguchi
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  4. A. Masuda
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  5. T. Nishikawa
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  6. M. Kobayashi
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Correspondence to T. Yamamoto.

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Yamamoto, T., Shirakawa, A., Kawaguchi, M. et al. Lytic infection of Epstein-Barr virus (EBV) in hemophagocytic syndrome associated with EBV-induced lymphoproliferative disorder. Ann Hematol 83, 127–132 (2004). https://doi.org/10.1007/s00277-003-0776-0

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  • DOI: https://doi.org/10.1007/s00277-003-0776-0

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