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Fatal Hodgkin and Non-Hodgkin Lymphoma Associated with Persistent Epstein-Barr Virus in Four Brothers

Rosemarie Donhuijsen-Ant, MD; Hinrich Abken, MD; Georg Bornkamm, MD; Konrad Donhuijsen, MD; Hans Grosse-Wilde, MD; Dieter Neumann-Haefelin, MD; Martin Westerhausen, MD; and Helga Wiegand, MD
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Requests for Reprints: R. Donhuijsen-Ant, MD, Department of Hematology/Oncology/Immunology, St. Johannes-Hospital, An der Abtei 7-11, 4100 Duisburg 11, Federal Republic of Germany.

Current Author Addresses: Drs. Donhuijsen-Ant and Westerhausen: Department of Hematology/Oncology/Immunology, St. JohannesHospital, An der Abtei 7-11, 4100 Duisburg 11, Federal Republic of Germany.

Dr. Abken: Institute of Genetics, Römer Str. 164, 5300 Bonn 1, Federal Republic of Germany.

Drs. Bornkamm, Neumann-Haefelin, and Wiegard: Department of Virology, Institute for Microbiology and Hygiene, Albert-Ludwigs University, Hermann-Herder Str. 11, 7800 Freiburg im Breisgau, Federal Republic of Germany.

Dr. Donhuijsen: Institute of Pathology, University of Essen, Hufelandstr. 55, 4300 Essen 1, Federal Republic of Germany.

Dr. Grosse-Wilde: Department of Immunogenetics, University of Essen, Virchowstrasse 171, 4300 Essen 1, Federal Republic of Germany.

© 1988 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1988;109(12):946-952. doi:10.7326/0003-4819-109-12-946
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Three brothers from one family died of Hodgkin disease and a fourth brother from a diffuse malignant non-Hodgkin lymphoma. This patient exhibited a constant deficiency of serum immunoglobulins and elevated antibody titers to Epstein-Barr viral antigens. Epstein-Barr virus DNA sequences were detected in DNA isolated from lymph node biopsies from two of the patients. Initially, no abnormalities in the numbers of B and T cells could be detected. Peripheral blood lymphocytes of the patients did not react in the mixed lymphocyte culture assay. We suggest that an immune deficiency to Epstein-Barr virus may favor the proliferation of malignant lymphocytes after Epstein-Barr viral infection. Monoclonal lymphoid B cell lines established spontaneously in vitro from a lymph node biopsy specimen and from peripheral blood specimens from two of the patients. The cells harbor Epstein-Barr viral DNA sequences in multiple genome equivalents and express Epstein-Barr nuclear antigen. The cells contain a tenfold increased level of c-fgr-related RNA transcripts compared with peripheral blood lymphocytes of healthy adults. No obvious amplifications or translocations of the c-myc, c-abl, or c-fgr gene could be detected.





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