Infectious Mononucleosis Accompanied by Clonal Proliferation of EBV-infected Cells and Infection of CD8-positive Cells

Overview

Journal Int J Hematol

Specialty Hematology

Date 2014 Mar 20

PMID 24643771

Citations 7

Authors

Ayako Arai

Takeshi Yamaguchi

Honami Komatsu

Ken-Ichi Imadome

Morito Kurata

Kaoru Nagata

Osamu Miura

Affiliations

Soon will be listed here.

Abstract

A 22-year-old male was admitted for a sustained fever of 2 months, lymphadenopathy, and liver dysfunction. Anti-VCA-IgM antibody was positive, with elevated Epstein-Barr virus (EBV)-DNA load in the peripheral blood. Liver biopsy revealed infiltration of CD8-positive and EBV-positive cells. Most peripheral blood mononuclear cells (PBMCs) were also positive for CD8, and showed detectable levels of EBV-DNA. Monoclonal proliferation of EBV-infected cells was detected in the PBMCs by Southern blotting for EBV-terminal repeat (EBV-TR). Although EBV-positive T-cell lymphoproliferative disease (EBV-T-LPD) was suspected, the symptoms spontaneously resolved within 12 months. Anti-VCA-IgM antibody and the clonal band of EBV-TR were negative 1 year after the onset, while anti-EBNA antibody was positive. The final diagnosis was thus confirmed as infectious mononucleosis (IM). Our results indicate that EBV-infected CD8-positive cells and clonal proliferation of EBV-infected cells may be temporally detected in IM. EBV-T-LPDs should be carefully excluded in such cases.

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References

Leight E, Sugden B . EBNA-1: a protein pivotal to latent infection by Epstein-Barr virus. Rev Med Virol. 2000; 10(2):83-100. DOI: 10.1002/(sici)1099-1654(200003/04)10:2<83::aid-rmv262>3.0.co;2-t. View

Stinchcombe J, Bossi G, Booth S, Griffiths G . The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity. 2001; 15(5):751-61. DOI: 10.1016/s1074-7613(01)00234-5. View

FISCHER E, Delibrias C, Kazatchkine M . Expression of CR2 (the C3dg/EBV receptor, CD21) on normal human peripheral blood T lymphocytes. J Immunol. 1991; 146(3):865-9. View

Tabiasco J, Vercellone A, Meggetto F, Hudrisier D, Brousset P, Fournie J . Acquisition of viral receptor by NK cells through immunological synapse. J Immunol. 2003; 170(12):5993-8. DOI: 10.4049/jimmunol.170.12.5993. View

Raab-Traub N, Flynn K . The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell. 1986; 47(6):883-9. DOI: 10.1016/0092-8674(86)90803-2. View

Tokunaga M, Uemura Y, Tokudome T, Sato E . Epstein-Barr virus-infected T cells in infectious mononucleosis. Acta Pathol Jpn. 1993; 43(3):146-7. DOI: 10.1111/j.1440-1827.1993.tb01124.x. View

Kimura H, Ito Y, Kawabe S, Gotoh K, Takahashi Y, Kojima S . EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases. Blood. 2011; 119(3):673-86. DOI: 10.1182/blood-2011-10-381921. View

Hodges E, Krishna M, Pickard C, Smith J . Diagnostic role of tests for T cell receptor (TCR) genes. J Clin Pathol. 2002; 56(1):1-11. PMC: 1769865. DOI: 10.1136/jcp.56.1.1. View

Arai A, Imadome K, Watanabe Y, Yoshimori M, Koyama T, Kawaguchi T . Clinical features of adult-onset chronic active Epstein-Barr virus infection: a retrospective analysis. Int J Hematol. 2011; 93(5):602-609. DOI: 10.1007/s12185-011-0831-x. View

10.

Young K, Zhang D, Malik J, Williams E . Fulminant EBV-driven CD8 T-cell lymphoproliferative disorder following primary acute EBV infection: a unique spectrum of T-cell malignancy. Int J Clin Exp Pathol. 2008; 1(2):185-97. PMC: 2480557. View

11.

Heslop H . Biology and treatment of Epstein-Barr virus-associated non-Hodgkin lymphomas. Hematology Am Soc Hematol Educ Program. 2005; :260-6. DOI: 10.1182/asheducation-2005.1.260. View

12.

Arai A, Nogami A, Imadome K, Kurata M, Murakami N, Fujiwara S . Sequential monitoring of serum IL-6, TNF-α, and IFN-γ levels in a CAEBV patient treated by plasma exchange and immunochemotherapy. Int J Hematol. 2012; 96(5):669-73. DOI: 10.1007/s12185-012-1170-2. View

13.

Virelizier J, Lenoir G, Griscelli C . Persistent Epstein-Barr virus infection in a child with hypergammaglobulinaemia and immunoblastic proliferation associated with a selective defect in immune interferon secretion. Lancet. 1978; 2(8083):231-4. DOI: 10.1016/s0140-6736(78)91744-0. View

14.

Sandberg Y, van Gastel-Mol E, Verhaaf B, Lam K, van Dongen J, Langerak A . BIOMED-2 multiplex immunoglobulin/T-cell receptor polymerase chain reaction protocols can reliably replace Southern blot analysis in routine clonality diagnostics. J Mol Diagn. 2005; 7(4):495-503. PMC: 1888492. DOI: 10.1016/S1525-1578(10)60580-6. View

15.

Jones J, Shurin S, Abramowsky C, Tubbs R, Sciotto C, Wahl R . T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections. N Engl J Med. 1988; 318(12):733-41. DOI: 10.1056/NEJM198803243181203. View

16.

Plumbley J, Fan H, Eagan P, Ehsan A, Schnitzer B, Gulley M . Lymphoid tissues from patients with infectious mononucleosis lack monoclonal B and T cells. J Mol Diagn. 2002; 4(1):37-43. PMC: 1906975. DOI: 10.1016/S1525-1578(10)60678-2. View

17.

Anagnostopoulos I, Hummel M, Kreschel C, STEIN H . Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus. Blood. 1995; 85(3):744-50. View

18.

He H, Wang M, Huang W . Infectious mononucleosis mimicking malignant T-cell lymphoma in the nasopharynx: a case report and review of the literature. Int J Clin Exp Pathol. 2012; 6(1):105-9. PMC: 3515983. View