T-Cell Lymphomas Containing Epstein–Barr Viral DNA in Patients with Chronic Epstein–Barr Virus Infections

J. F. Jones, S. Shurin, C. Abramowsky, R. R. Tubbs, C. G. Sciotto, R. Wahl, J. Sands, D. Gottman, B. Z. Katz, J. Sklar

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506 Scopus citations

Abstract

Fatal T-cell lymphomas developed in three patients with a chronic illness manifested by fever, pneumonia, dysgammaglobulinemia, hematologic abnormalities, and extraordinarily high titers of antibody to the Epstein–Barr virus (EBV) capsid antigen (>10,000) and early antigen (>640) but low titers to the EBV nuclear antigen (≤40). To understand the pathogenesis of these tumors better, we determined the immunophenotype of the tumor cells and analyzed tumor-cell DNA for EBV genomes and for lymphoid-cell gene rearrangements. More than 80 percent of the cells in tumors had an activated helper T-cell phenotype (T4, T11, la positive). The EBV genome was found by in situ hybridization in tumor tissue from each patient. Southern blot assay of DNA digests from one patient showed the same pattern as that of the EBV-infected marmoset line, B95–8. DNA digests from two patients showed a monoclonal proliferation of T cells determined on the basis of uniform T-cell–receptor gene rearrangements and a single band for the joined termini of the EBV genome. We conclude that EBV may infect T cells and contribute to lymphomas in selected patients with severe EBV infections. (N Engl J Med 1988; 318:733–41.) THE Epstein–Barr virus (EBV) is classically associated with infectious mononucleosis and two neoplastic diseases, African Burkitt's lymphoma and nasopharyngeal carcinoma.1 More recently, it has been associated with lymphoproliferative disorders in primary and secondary immunodeficiency,2,3 in one case of thymic lymphoepithelial carcinoma,4 and with a variety of other non-neoplastic disorders having a number of unusual immunologic and hematologic features.5 6 7 Although many organ systems, including the liver and brain, are altered in these diseases, viral DNA has been found only in B lymphocytes,8 oropharyngeal epithelial cells,9 and salivary-gland duct cells,10 as well as in thymic lymphoepithelial carcinoma cells.4 Host responses to infection,.

Original languageEnglish (US)
Pages (from-to)733-741
Number of pages9
JournalNew England Journal of Medicine
Volume318
Issue number12
DOIs
StatePublished - Mar 24 1988

ASJC Scopus subject areas

  • Medicine(all)

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