Skip to main content

Advertisement

Log in

Flow cytometric analysis of skin blister fluid induced by mosquito bites in a patient with chronic active Epstein–Barr virus infection

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

In chronic active Epstein–Barr virus (EBV) infection (CAEBV), ectopic EBV infection has been described in T or natural killer (NK) cells. NK cell-type infection (NK-CAEBV) is characterized by large granular lymphocytosis, high IgE levels and unusual reactions to mosquito bites, including severe local skin reactions, fever and liver dysfunction. However, the mechanisms underlying these reactions remain undetermined. Herein, we describe a patient with NK-CAEBV whose blister fluid after mosquito bites was analyzed. The patient exhibited significant increases in the percentage of CD56+ NK cells in the fluid compared with a simple mosquito allergy, in which the majority of infiltrated cells were CD203c+ cells, indicating basophils and/or mast cells. His fluid also contained CD203c+ cells, and his circulating basophils were activated by mosquito extracts in vitro. These results suggest that CD203c+ cells as well as NK cells may play pathogenic roles in the severe skin reactions to mosquito bites in NK-CAEBV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hislop AD, Taylor GS, Sauce D, Rickinson AB. Cellular responses to viral infection in humans: lessons from Epstein–Barr virus. Annu Rev Immunol. 2007;25:587–617.

    Article  CAS  PubMed  Google Scholar 

  2. Kutok JL, Wang F. Spectrum of Epstein–Barr virus-associated diseases. Annu Rev Pathol. 2006;1:375–404.

    Article  CAS  PubMed  Google Scholar 

  3. Yachie A, Kanegane H, Kasahara Y. Epstein–Barr virus-associated T-/natural killer cell lymphoproliferative diseases. Semin Hematol. 2003;40:124–32.

    Article  PubMed  Google Scholar 

  4. Okano M, Kawa K, Kimura H, et al. Proposed guidelines for diagnosing chronic active Epstein–Barr virus infection. Am J Hematol. 2005;80:64–9.

    Article  PubMed  Google Scholar 

  5. Kimura H, Hoshino Y, Hara S, et al. Differences between T cell-type and natural killer cell-type chronic active Epstein–Barr virus infection. J Infect Dis. 2005;191:531–9.

    Article  CAS  PubMed  Google Scholar 

  6. Peng Z, Simons FE. Advances in mosquito allergy. Curr Opin Allergy Clin Immunol. 2007;7:350–4.

    Article  CAS  PubMed  Google Scholar 

  7. Lima M, Almeida J, dos Anjos Teixeira M, Queiros ML, Justica B, Orfao A. The “ex vivo” patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR expression identify acute/early and chronic/late NK-cell activation states. Blood Cells Mol Dis. 2002;28:181–90.

    Article  PubMed  Google Scholar 

  8. Wada T, Kurokawa T, Toma T, et al. Immunophenotypic analysis of Epstein-Barr virus (EBV)-infected CD8(+) T cells in a patient with EBV-associated hemophagocytic lymphohistiocytosis. Eur J Haematol. 2007;79:72–5.

    Article  CAS  PubMed  Google Scholar 

  9. Kasahara Y, Yachie A, Takei K, et al. Differential cellular targets of Epstein–Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Blood. 2001;98:1882–8.

    Article  CAS  PubMed  Google Scholar 

  10. Wada T, Schurman SH, Otsu M, Garabedian EK, Ochs HD, Nelson DL, et al. Somatic mosaicism in Wiskott–Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism. Proc Natl Acad Sci USA. 2001;98:8697–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hauswirth AW, Natter S, Ghannadan M, et al. Recombinant allergens promote expression of CD203c on basophils in sensitized individuals. J Allergy Clin Immunol. 2002;110:102–9.

    Article  CAS  PubMed  Google Scholar 

  12. Pacheco SE, Gottschalk SM, Gresik MV, Dishop MK, Okmaura T, McCormick TG. Chronic active Epstein–Barr virus infection of natural killer cells presenting as severe skin reaction to mosquito bites. J Allergy Clin Immunol. 2005;116:470–2.

    Article  PubMed  Google Scholar 

  13. Satoh M, Oyama N, Akiba H, Ohtsuka M, Iwatsuki K, Kaneko F. Hypersensitivity to mosquito bites with natural-killer cell lymphocytosis: the possible implication of Epstein–Barr virus reactivation. Eur J Dermatol. 2002;12:381–4.

    PubMed  Google Scholar 

  14. Asada H, Miyagawa S, Sumikawa Y, et al. CD4+ T-lymphocyte-induced Epstein–Barr virus reactivation in a patient with severe hypersensitivity to mosquito bites and Epstein–Barr virus-infected NK cell lymphocytosis. Arch Dermatol. 2003;139:1601–7.

    Article  PubMed  Google Scholar 

  15. Tokura Y, Matsuoka H, Koga C, Asada H, Seo N, Ishihara S, et al. Enhanced T-cell response to mosquito extracts by NK cells in hypersensitivity to mosquito bites associated with EBV infection and NK cell lymphocytosis. Cancer Sci. 2005;96:519–26.

    Article  CAS  PubMed  Google Scholar 

  16. Peng Z, Li H, Simons FE. Immunoblot analysis of salivary allergens in 10 mosquito species with worldwide distribution and the human IgE responses to these allergens. J Allergy Clin Immunol. 1998;101:498–505.

    Article  CAS  PubMed  Google Scholar 

  17. Gane P, Pecquet C, Crespeau H, Lambin P, Leynadier F, Rouger P. Flow cytometric monitoring of allergen-induced basophil activation. Cytometry. 1995;19:361–5.

    Article  CAS  PubMed  Google Scholar 

  18. Karasuyama H, Mukai K, Tsujimura Y, Obata K. Newly discovered roles for basophils: a neglected minority gains new respect. Nat Rev Immunol. 2009;9:9–13.

    Article  CAS  PubMed  Google Scholar 

  19. Watanabe M, Satoh T, Yamamoto Y, Kanai Y, Karasuyama H, Yokozeki H. Overproduction of IgE induces macrophage-derived chemokine (CCL22) secretion from basophils. J Immunol. 2008;181:5653–9.

    Article  CAS  PubMed  Google Scholar 

  20. Inngjerdingen M, Damaj B, Maghazachi AA. Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309. J Immunol. 2000;164:4048–54.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from Mitsubishi Pharma Research Foundation, Osaka; a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and a grant from the Ministry of Health, Labour and Welfare of Japan, Tokyo. We thank Ms Harumi Matsukawa and Ms. Shizu Kouraba for their excellent technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Taizo Wada.

About this article

Cite this article

Wada, T., Yokoyama, T., Nakagawa, H. et al. Flow cytometric analysis of skin blister fluid induced by mosquito bites in a patient with chronic active Epstein–Barr virus infection. Int J Hematol 90, 611–615 (2009). https://doi.org/10.1007/s12185-009-0442-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-009-0442-y

Keywords

Navigation