In patients with Hodgkin's disease, titers of IgG antibody against viral capsid antigen of Epstein-Barr virus and the prevalence of antibodies against early antigen are higher than expected. To evaluate whether this condition antedates diagnosis, we identified 43 persons with Hodgkin's disease, from whom blood had been drawn and stored for an average of 50.5 months before diagnosis, and 96 controls from the same populations, from whom blood had been drawn at the same time. The relative risks of Hodgkin's disease associated with elevated levels of IgG and IgA antibodies against capsid antigen were 2.6 (90 percent confidence interval, 1.1 to 6.1) and 3.7 (1.4 to 9.3), respectively. For Epstein-Barr nuclear antigen, the relative risk was 4.0 (1.4 to 11.4), and for early antigen D it was 2.6 (1.1 to 6.1). However, the prevalence of IgM antibody against capsid antigen was substantially lower in patients with Hodgkin's disease (0.22 [0.04 to 1.3]). These associations were stronger in serum samples obtained at least three years before diagnosis than in serum samples obtained closer to diagnosis. We conclude that the development of Hodgkin's disease may in some patients be preceded by enhanced activation of Epstein-Barr virus. Whether Epstein-Barr virus has a direct role in the pathogenesis of the disease or is simply a marker for a more fundamental factor affecting the immune control of latent infections is unknown.
Source Information
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115.
This article has been cited by other articles:
(2008). Honors and Awards * Bibliography of Peer-Reviewed Journal Articles. Am J Epidemiol
168: 845-854
[Full Text]
Nieters, A., Rohrmann, S., Becker, N., Linseisen, J., Ruediger, T., Overvad, K., Tjonneland, A., Olsen, A., Allen, N. E., Travis, R. C., Bingham, S., Khaw, K.-T., Ardanaz, E., Redondo, M. L., Basterrechea, M., Martinez, C., Tormo, M.-J., Rosso, S., Tagliabue, G., Masala, G., Mattiello, A., Tumino, R., Boeing, H., Bergmann, M., Kaaks, R., Trichopoulou, A., Trichopoulos, D., Peeters, P. H., Bueno-de-Mesquita, B., Boffetta, P., Brennan, P., Ferrari, P., Neasham, D., Lund, E., Berglund, G., Manjer, J., Hallmans, G., Johansson, I., Vineis, P., Riboli, E.
(2008). Smoking and Lymphoma Risk in the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol
167: 1081-1089
[Abstract][Full Text]
Ambinder, R. F.
(2008). Hodgkin twins: double good, double trouble. Blood
111: 3310-3310
[Full Text]
Kapatai, G, Murray, P
(2007). Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma. J. Clin. Pathol.
60: 1342-1349
[Abstract][Full Text]
Hjalgrim, H., Ekstrom-Smedby, K., Rostgaard, K., Amini, R.-M., Molin, D., Hamilton-Dutoit, S., Schollkopf, C., Chang, E. T., Ralfkiaer, E., Adami, H.-O., Glimelius, B., Melbye, M.
(2007). Cigarette Smoking and Risk of Hodgkin Lymphoma: A Population-Based Case-Control Study. Cancer Epidemiol. Biomarkers Prev.
16: 1561-1566
[Abstract][Full Text]
Hjalgrim, H., Ekstrom Smedby, K., Rostgaard, K., Molin, D., Hamilton-Dutoit, S., Chang, E. T., Ralfkiaer, E., Sundstrom, C., Adami, H.-O., Glimelius, B., Melbye, M.
(2007). Infectious Mononucleosis, Childhood Social Environment, and Risk of Hodgkin Lymphoma. Cancer Res.
67: 2382-2388
[Abstract][Full Text]
Besson, C., Amiel, C., Le-Pendeven, C., Brice, P., Ferme, C., Carde, P., Hermine, O., Raphael, M., Abel, L., Nicolas, J.-C.
(2006). Positive Correlation between Epstein-Barr Virus Viral Load and Anti-Viral Capsid Immunoglobulin G Titers Determined for Hodgkin's Lymphoma Patients and Their Relatives. J. Clin. Microbiol.
44: 47-50
[Abstract][Full Text]
Clarke, C. A., Glaser, S. L., Keegan, T. H.M., Stroup, A.
(2005). Neighborhood Socioeconomic Status and Hodgkin's Lymphoma Incidence in California. Cancer Epidemiol. Biomarkers Prev.
14: 1441-1447
[Abstract][Full Text]
Levin, L. I., Munger, K. L., Rubertone, M. V., Peck, C. A., Lennette, E. T., Spiegelman, D., Ascherio, A.
(2005). Temporal Relationship Between Elevation of Epstein-Barr Virus Antibody Titers and Initial Onset of Neurological Symptoms in Multiple Sclerosis. JAMA
293: 2496-2500
[Abstract][Full Text]
Chang, E. T., Zheng, T., Weir, E. G., Borowitz, M., Mann, R. B., Spiegelman, D., Mueller, N. E.
(2004). Childhood Social Environment and Hodgkin's Lymphoma: New Findings from a Population-Based Case-Control Study. Cancer Epidemiol. Biomarkers Prev.
13: 1361-1370
[Abstract][Full Text]
Chang, E. T., Montgomery, S. M., Richiardi, L., Ehlin, A., Ekbom, A., Lambe, M.
(2004). Number of Siblings and Risk of Hodgkin's Lymphoma. Cancer Epidemiol. Biomarkers Prev.
13: 1236-1243
[Abstract][Full Text]
Chang, Y., Chang, S.-S., Lee, H.-H., Doong, S.-L., Takada, K., Tsai, C.-H.
(2004). Inhibition of the Epstein-Barr virus lytic cycle by Zta-targeted RNA interference. J. Gen. Virol.
85: 1371-1379
[Abstract][Full Text]
Hjalgrim, H., Rasmussen, S., Rostgaard, K., Nielsen, N. M., Koch-Henriksen, N., Munksgaard, L., Storm, H. H., Melbye, M.
(2004). Familial Clustering of Hodgkin Lymphoma and Multiple Sclerosis. JNCI J Natl Cancer Inst
96: 780-784
[Abstract][Full Text]
Glaser, S. L., Hsu, J. L., Gulley, M. L.
(2004). Epstein-Barr Virus and Breast Cancer: State of the Evidence for Viral Carcinogenesis. Cancer Epidemiol. Biomarkers Prev.
13: 688-697
[Abstract][Full Text]
Cozen, W., Gill, P. S., Ingles, S. A., Masood, R., Martinez-Maza, O., Cockburn, M. G., Gauderman, W. J., Pike, M. C., Bernstein, L., Nathwani, B. N., Salam, M. T., Danley, K. L., Wang, W., Gage, J., Gundell-Miller, S., Mack, T. M.
(2004). IL-6 levels and genotype are associated with risk of young adult Hodgkin lymphoma. Blood
103: 3216-3221
[Abstract][Full Text]
Moody, C. A., Scott, R. S., Su, T., Sixbey, J. W.
(2003). Length of Epstein-Barr Virus Termini as a Determinant of Epithelial Cell Clonal Emergence. J. Virol.
77: 8555-8561
[Abstract][Full Text]
Lehtinen, M., Koskela, P., Ogmundsdottir, H. M., Bloigu, A., Dillner, J., Gudnadottir, M., Hakulinen, T., Kjartansdottir, A., Kvarnung, M., Pukkala, E., Tulinius, H., Lehtinen, T.
(2003). Maternal Herpesvirus Infections and Risk of Acute Lymphoblastic Leukemia in the Offspring. Am J Epidemiol
158: 207-213
[Abstract][Full Text]
Levin, L. I., Munger, K. L., Rubertone, M. V., Peck, C. A., Lennette, E. T., Spiegelman, D., Ascherio, A.
(2003). Multiple Sclerosis and Epstein-Barr Virus. JAMA
289: 1533-1536
[Abstract][Full Text]
Ascherio, A., Munger, K. L., Lennette, E. T., Spiegelman, D., Hernan, M. A., Olek, M. J., Hankinson, S. E., Hunter, D. J.
(2001). Epstein-Barr Virus Antibodies and Risk of Multiple Sclerosis: A Prospective Study. JAMA
286: 3083-3088
[Abstract][Full Text]
Nakamura, H., Zarycki, J., Sullivan, J. L., Jung, J. U.
(2001). Abnormal T Cell Receptor Signal Transduction of CD4 Th Cells in X-Linked Lymphoproliferative Syndrome. J. Immunol.
167: 2657-2665
[Abstract][Full Text]
Chu, P. G., Chang, K. L., Chen, Y.-Y., Chen, W.-G., Weiss, L. M.
(2001). No Significant Association of Epstein-Barr Virus Infection with Invasive Breast Carcinoma. Am. J. Pathol.
159: 571-578
[Abstract][Full Text]
Alexander, F. E., Jarrett, R. F., Cartwright, R. A., Armstrong, A. A., Gokhale, D. A., Kane, E., Gray, D., Lawrence, D. J., Taylor, G. M.
(2001). Epstein-Barr Virus and HLA-DPB1-*0301 in Young Adult Hodgkin's Disease: Evidence for Inherited Susceptibility to Epstein-Barr Virus in Cases that Are EBV+ve. Cancer Epidemiol. Biomarkers Prev.
10: 705-709
[Abstract][Full Text]
Spieker, T., Kurth, J., Kuppers, R., Rajewsky, K., Brauninger, A., Hansmann, M.-L.
(2000). Molecular single-cell analysis of the clonal relationship of small Epstein-Barr virus-infected cells and Epstein-Barr virus-harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease. Blood
96: 3133-3138
[Abstract][Full Text]
Flavell, K J, Murray, P G
(2000). Hodgkin's disease and the Epstein-Barr virus. Mol. Pathol.
53: 262-269
[Abstract][Full Text]
Hjalgrim, H., Askling, J., Sorensen, P., Madsen, M., Rosdahl, N., Storm, H. H., Hamilton-Dutoit, S., Eriksen, L. S., Frisch, M., Ekbom, A., Melbye, M.
(2000). Risk of Hodgkin's Disease and Other Cancers After Infectious Mononucleosis. JNCI J Natl Cancer Inst
92: 1522-1528
[Abstract][Full Text]
Cohen, J. I.
(2000). Epstein-Barr Virus Infection. NEJM
343: 481-492
[Full Text]
Quintanilla-Martinez, L., Kumar, S., Fend, F., Reyes, E., Teruya-Feldstein, J., Kingma, D. W., Sorbara, L., Raffeld, M., Straus, S. E., Jaffe, E. S.
(2000). Fulminant EBV+ T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome. Blood
96: 443-451
[Abstract][Full Text]
Damania, B., Choi, J.-K., Jung, J. U.
(2000). Signaling Activities of Gammaherpesvirus Membrane Proteins. J. Virol.
74: 1593-1601
[Full Text]
Ambinder, R. F.
(2000). Gammaherpesviruses and ""Hit-and-Run"" Oncogenesis. Am. J. Pathol.
156: 1-3
[Full Text]
Franchini, G., Ambinder, R. F., Barry, M.
(2000). Viral Disease in Hematology. ASH Education Book
2000: 409-423
[Abstract][Full Text]
Chang, K. L., Chen, Y.-Y., Chen, W.-G., Hayashi, K., Bacchi, C., Bacchi, M., Weiss, L. M.
(1999). EBNA-1 Gene Sequences in Brazilian and American Patients With Hodgkin's Disease. Blood
94: 244-250
[Abstract][Full Text]
Skolnik, P. R., Mark, E. J.
(1999). Case 5-1999- A 37-Year-Old Man with Fever and Diffuse Lymphadenopathy. NEJM
340: 545-554
[Full Text]
Kim, S. H., Choi, E. Y., Shin, Y. K., Kim, T. J., Chung, D. H., Chang, S. I., Kim, N. K., Park, S. H.
(1998). Generation of Cells With Hodgkin's and Reed-Sternberg Phenotype Through Downregulation of CD99 (Mic2). Blood
92: 4287-4295
[Abstract][Full Text]
Murray, P. G., Constandinou, C. M., Crocker, J., Young, L. S., Ambinder, R. F.
(1998). Analysis of Major Histocompatibility Complex Class I, TAP Expression, and LMP2 Epitope Sequence in Epstein-Barr Virus-Positive Hodgkin's Disease. Blood
92: 2477-2483
[Abstract][Full Text]
Quintanilla-Martinez, L., Lome-Maldonado, C., Ott, G., Gschwendtner, A., Gredler, E., Reyes, E., Angeles-Angeles, A., Fend, F.
(1997). Primary Non-Hodgkin's Lymphoma of the Intestine: High Prevalence of Epstein-Barr Virus in Mexican Lymphomas as Compared With European Cases. Blood
89: 644-651
[Abstract][Full Text]
Mack, T. M., Cozen, W., Shibata, D. K., Weiss, L. M., Nathwani, B. N., Hernandez, A. M., Taylor, C. R., Hamilton, A. S., Deapen, D. M., Rappaport, E. B.
(1995). Concordance for Hodgkin's Disease in Identical Twins Suggesting Genetic Susceptibility to the Young-Adult Form of the Disease. NEJM
332: 413-419
[Abstract][Full Text]