LOS VIRUS HERPES HUMANOS 4 (VIRUS DE EPSTEIN BARR/VEB) Y 6 (HHV-6) EN LAS ENFERMEDADES DE HODGKIN Y DE KIKUCHI, Y SU RELACION CON PROLIFERACION Y APOPTOSIS

(especial para SIIC © Derechos reservados)
La Enfermedad de Hodgkin está frecuentemente infectada tanto por Virus Epstein Barr como por Herpes Virus 6 mientras que la Enfermedad de Kikuchi tiende a estar infectada únicamente por el Herpes Virus 6.
rojo9.jpg Autor:
Julieta Rojo
Columnista Experto de SIIC
Artículos publicados por Julieta Rojo
Coautores
Mónica Romero (MD)*  Humberto Cruz-Ortíz (MD)*  Marie Luise Huetter (MD)**  Birgit Gathof (MD)***  GRF Krueger (MD)**** 
Hospital General de México, O.D. Depto. de Salud Pública y Unidad de Patología , Facultad de Medicina de la Universidad Nacional Autónoma de México (UNAM)*
Laboratorio de Inmunopatología, Clínica Universidad de Colonia, Alemania**
Medicina Transfusional. Clínica de la Universidad de Colonia, Alemania.***
Instituto de Anatomía. Universidad de Colonia,Alemania.****
Recepción del artículo
17 de Noviembre, 2003
Aprobación
5 de Enero, 2004
Primera edición
10 de Febrero, 2004
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
Antecedentes. El virus de Epstein Barr (VEB) y el herpesvirus humano tipo 6 HHV-6 se encuentran frecuentemente asociados a la enfermedad de Hodgkin (EH) y en algunos casos a la de Kikuchi Fujimoto (EKF). Ambos tienen una relación aparente con procesos de proliferación o de apoptosis como lo representan la EH y EKF respectivamente. Objetivo. En el presente trabajo investigamos la frecuencia y localización de la expresión antigénica y del ADN de ambos virus en cortes de tejido de EH y EKF en relación a marcadores de proliferación celular y de apoptosis. Método. Se revisaron las biopsias de ganglios de 84 pacientes del Hospital General de México y de 26 de la Clínica de la Universidad de Colonia con EH y 14 con EKF; todas fueron investigadas inmunohistológicamente para expresión antigénica viral (VEB: LMP-1: HHV-6 gp110/60), Ki67/PCNA, marcador de proliferación (MIB1)/p53 y WAF1 para apoptosis. El ADN viral se demostró por hibridación in situ. La apoptosis se demostró con las técnicas de ISEL y TUNEL. Resultados. La EH está frecuentemente infectada tanto por VEB como por HHV-6 mientras que la EKF tiende a estar infectada únicamente por el HHV-6. El VEB está presente en la EH en las células de Hodgkin y de Reed-Sternberg y el HHV-6 en linfocitos e histiocitos de ambas enfermedades. El marcador de proliferación celular se encontró en ambas enfermedades . La apoptosis se demostró principalmente en la EKF y menos en la EH. Conclusión. Aun cuando el VEB y el HHV-6 pueden no ser abiertamente oncogénicos en la EH y la EKF, pueden influir en el curso de la enfermedad. La infección dual en la EH parece apoyar más el proceso de proliferación, con predominio del efecto del VEB. La infección por HHV-6 en la EKF parece favorecer el curso apoptósico. Estos efectos son -de acuerdo con la literatura- posiblemente mediados por citocinas.

Palabras clave
Enfermedad de Hodgkin, enfermedad de Kikuchi-Fujimoto, virus de Epstein Barr (VEB), virus herpes humano-6 (HHV6), apoptosis, proliferación


Artículo completo

(castellano)
Extensión:  +/-7.12 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
Background: Epstein Barr virus/EBV and HHV-6 are frequently found in Hodgkin's disease (HD) and -to a certain extent- in Kikuchi-Fujimoto's disease (KFD). Both viruses are apparently related to proliferative and/or apoptotic processes as represented by HD or KFD respectively. Objective: To correlate frequency and location of antigen and DNA expression of both viruses in HD or KFD tissue sections in relation to markers for cell proliferation and apoptosis. Design: Archival lymph node biopsies from 84 patients from the Hospital General de Mexico and 26 from the Clinic of the University of Cologne, Germany with HD and 14 with KFD were investigated immunhistologically for viral antigen expression (EBV LMP-1: HHV-6 gp110/60), Ki67/PCNA marker for proliferation (MIB1)/p53 and WAF1 for apoptosis. Viral ADN was shown by in situ hybridization. Apoptosis was determined by ISEL and TUNEL techniques. Results: HD is frequently infected by both EBV and HHV-6 while KFD tends to be infected only by HHV-6. EBV and HD is present in HD cells and Reed-Sternberg cells, HHV-6 preferentially in lymphocytes and in histiocytes in both HD and in KFD. Proliferation marker is found in both diseases. Apoptosis is demonstrated preferentially in KFD and to a lesser extent also in HD. Conclusion: Although EBV and HHV-6 may not be openly oncogenic in HD and KFD, they may well influence the course of the disease. Dual infection in HD appears to support proliferative processes,i.e. a predominance of EBV effects. Single infection with HHV-6 in KFD instead appears to favor an apoptotic course. These effects are- according to the literature-possibly cytokine-mediated.

Key words
Hodgkin disease, Kikuchi Fujimoto disease, Epstein Barr Virus (EVB), human Herpesvirus-6 (HHV-6), apoptosis, proliferation


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Oncología
Relacionadas: Anatomía Patológica, Hematología, Infectología, Medicina Interna



Comprar este artículo
Extensión: 7.12 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra




Patrocinio y reconocimiento:
Este trabajo fue realizado en parte gracias al apoyo del Servicio Alemán de Intercambio Académico (DAAD).
Bibliografía del artículo
  1. Dorfman RF, Berry GJ: Kikuchi's histiocytic necrotizing lymphadenitis: an analysis of 108 cases with emphasis on differential diagnosis,Semin Diagn Pathol 1988; 5:329-45
  2. Fischer R, Krueger GRF: Problems in classification and differential diagnosis of Hodgkin's disease. Internist 1981; 22:255-63
  3. Kikuchi M: Lymphadenitis showing focal reticulum cell hyperplasia with nuclear debris and phagocytes. Acta Haematol Jpn 1972; 35:379-80
  4. Lukes RJ, Butler JJ: Pathology and nomenclature of Hodgkin's disease. Cancer res 1966; 26 1063-83
  5. Jaffet RF. Viruses and Hodgkin's Lymphoma. Ann Oncol 2002; 13 Supll 1:23-9
  6. Kikuchi M, Sumiyoshi Y, Minamishima Y: Kikuchi's disease (histocytic necrotizing Lymphadenitis. In: Ablashi DV, Krueger GRF, Salahuddin SZ. Human Herpesvirus-6. Epidemiology molecular biology and clinical pathology. Elsevier,Amsterdam , 1992.
  7. Krueger GRF, Ferrer Argote V. A unifying concept of viral immunopathogenesis of proliferative and aproliferative diseases. A working hypothesis. In Vivo 1994; 8:493-500
  8. Kim E, Krueger E, Boehmer S, Klussmann JP, Krueger GRF. In vitro cytobiological effects of human herpesvirus 6 and 7: immunohistological monitoring of apoptosis. Differentiation and cell proliferation. Anticancer Res 1997; 17: 4623-32
  9. Krueger GRF, Buja LM, Rojo J, Lasch J, Koch B, Leyssens N: Apoptosis and proliferation in HHV-6 infection. Pathologe 1995; 16:120-7
  10. Epstein, M.A., Achong, B.G. and Barr, Y. M.. Virus particles in cultures lymphoblasts from Burkitt´s lymphoma. Lancet, 1964, 1, 702.
  11. Craig, F.E., Gulley, M.L. and Banks, P.M.. Postransplantation lymphoproliferative disorders. Am. J. Clin. Phatol. 1993, 99; 265-271.
  12. Kanavaros, P., de Bruin, P.C., Briere, J., Meijer, C.J.L. M. and Gaulard, P. Epstein-Barr virus (EBV) in extranodal T-cell non-Hodgkin´s lymphoma (T-NHL). Identification of nasal T-NHL as a distinct clinocopathological entity associated with EBV. Leukem. Lymphoma, 1995 ;18, 27-34.
  13. Anagnostopoulos I, Hummel M: Epstein Barr virus in tumours. Histopathology, 1996; 29: 297-315.
  14. Quintanilla Martínez L, Gamboa Domínguez A, Goméz-Ledezma I, et al: Association of Epstein-Barr virus latent membrane protein and Hodgkin¨s disease in México. Mod Pathol, 1995; 8, 675-679.
  15. Zarate Osorno A, Roman L.N., Kingma DW, et al: Hodgkin s disease in Mexico. Prevalence of Epstein-Barr virus sequences and correlation with histologic subtyp. Cancer, 1995;75: 1360-1366
  16. Cordova Perez FJ, González-Keelan CI, Velez R. Epstein- Barr virus in biopsies from patients with Hodgkin and non-Hodgkin lymphoma at the University of Puerto Rico immunohistochemistry laboratory. P R Health Sci J 2003; 22(2):125-9
  17. Ambinder RF, Browning PJ, Lorenzana I, et al: Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United S tates. Blood, 1993; 81: 462-467
  18. Yamanishi K, Okuno T, Shiraki, Takahashi M, Asano Y, Kurata T: Identification of human herpesvirus 6 as casual agent for exanthem subitum. Lancet, 1988;1: 1065.
  19. Torelli Giuseppe, Marasca Roberto, Luppi Mario, Selleri Licia, Ferrari Sergio, Norni Franco and cols: Human Herpesvirus-6 in Human Lymphomas: Identification of specific sequences in Hodgkin's Lymphomas by polymerasa chain reaction. Blood 1991;77:10; 2251-2258
  20. Dirnhofer Stephan, Angeles Angeles Arturo, Ortíz-Hidalgo Carlos, Reyes Edgardo, Gredler Evelyn and cols. High prevalence of a 30 Base Pair Deletion in the Epstein-Barr virus (EBV) Latent Membrane Protein 1 Gene and of Strain Type B EBV in Mexican Clasical Hodgkin's Disease and Reactive Lymphoid Tissue. Human Pathology 1999;30: 781-787
  21. Henle W, Henle GE, Horwitz CA. Epstein- Barr virus specific diagnostic tests in Infectious mononucleosis. Hum Pathol 1974; 5:551-65
  22. Krueger GRF, Ablashi DV, Jospephs SF, Salahuddin SZ, Lembke U, Ramon A, Bertram G. Clinical indications and diagnostic techniques of human hepresvirus-6 (HHV-6) infection. In Vivo 1991; 5 :287-96
  23. Krueger GRF, Guenther A, Knueffermann R, Klueppelberg U, Luka J, Pearson GR, Ablashi DV, Juecker M, Tesch H. Human herpesvirus-6 (HHV-6) in Hodgkin's disease: cellular expression of viral antigens, as compared to oncogens met and fes , tumor suppressor gene product p53, and interleukins 2 and 6. In Vivo 1994; 8: 501-16
  24. Chang KL, Albajar PF, Chen Y-Y, Johnson RM, Weiss LM: High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of Hodgkin's disease ocurring in Peru. Blood, 1993;81: 496-499
  25. Flavell KJ, Billingham LJ, Biddulph JP, Gray L, Flavell JR, Constandinou CM, Young LS, Murray PG. The effect of Epstein- Barr virus status on outcome in age- and sex- defined subgroups of patients with advanced Hodgkin's disease. Ann Oncol 2003; 14(2): 282-90
  26. Armstrong A, Jarret R, Lennard A, Proctor S, Angus B: Hodgkin's disease and EBV: prognostic significance of EBV positivity. J Pathol, 1992;167: 124.
  27. Vestlev PM, Pallesen G, Sandvej K, Hamilton-Dutoit SJ, Bendtzen SM: Prognosis of Hodgkin's disease is not influenced by Epstein-Barr virus latent membrane protein (letter). Int J Cancer, 1992;50:670.
  28. Serraino D, Franceschi S, Talamini R, Barra S, Negri E, Carbone A, La Vecchi C: Socioeconomic indicators, infectious disease and Hodgkin's disease. Int J Cancer, 1991;47:352.
  29. Niller HH, Salamon D, Ilg K, Koroknai A, Banati F, Bauml G, Rucker O, Schwarzmann F, Wolf H, Minarovits J. The in vivo binding site for oncoprotein-cMyc in the promoter for Epstein-Barr virus (EBV) encoding RNA (EBER) 1 suggests a specific role for EBV in lymphomagenesis. Med Sci Monit 2003; 9(1): HY1-9
  30. Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene 2003; 22 (33): 5108-21
  31. Boyle MJ, Vasak E,Tschuchnigg M, Turner JJ, Sculley T, Pennny R, Cooper DA, Tindall B, Sewell WA: Subtypes of Epstein-Barr virus (EBV) in Hodgkin's disease: association between B-type EBV and immunocompromise. Blood, 1993;81:468.
  32. Luppi M, Marasca R, Barozzi P, Artusi T, Torelli G: Frequent detection of human herpesvirus-6 sequences by polymerasa chain reaction in paraffin-embedded lymph nodes from patientes with angioimmunoblastic lymphadenopaty-like lymphoma. Leuk Res 1993; 17:1003-1011.
  33. Josephs SF, Buchbinder A, Streicher HZ, Ablashi DV, Salahuddin SZ, Guo H-G, Wong Staal F, Cossman J, Raffeld M, Sundeen J, Levine P, Biggar R, Krueger GRF , Fox RI, Gallo RC: Deteccion of human B lymphotropic virus (human herpesvirus 6) sequences in B lymphoma tissues of three patientes. Leuk 1988; 2: 496-502.
  34. Flamand L; Gosselin J, Stefanescu I, Ablashi DV, Menezes J. Immunosupressive effect of human herpesvirus-6 on T cell functions: supression of interleukin-2 synthesis and cell proliferation. Blood 1995; 85: 1263-71
  35. Oshima K, Kikuchi M, Sumiyoshi Y, Masuda Y, Mohtai H, Eguchi F, Takehita M,. Proliferating cells in histiocytic necrotizing lymphadenitis. Virchows Arch B Cell Pathol Incl Mol Pathol 1992; 61: 97-100
  36. Iguchi H, Sunami K, Yamane H, Konishi K, Takayama M, Nakai Y, Nakagawa T, Shibata S, Nishimura K. Apoptotic cell death in Kikuchi's disease: a TEM study. Acta Otolaryngol 1998; 538 (suppl):250-3
  37. Liu Q, Oshima K, Shinohara T, Kikuchi M. Apotosis in histiocytic necrotizing lymphadenitis. Pathol Int 1995; 45:729-34
  38. Ura H, Yamada N, Torii H, Imakado S, Iozumi K, Shimada S. Histiocytic necrotizing Lymphadenitis (Kikuchi's disease): the necrotic appearance of the lymph node cells is caused by apoptosis. J Dermatol 1999; 26: 385-9
  39. Gold R, Schmied M, Giegerich G, Breitschopf H, Hartung HP, Toyka KV, Lassmann H. Differentiation between cellular apoptosis and necrosis by the combined use of in situ tailing and nick translation techniques .Lab Invest 1994; 71:219-225
  40. Krueger GRF, Schonnebeck M, Braun M. Changes in cell membrane fluidity and in receptor expression following infections with HHV-6 may influence superinfection with other viruses. AIDS Res Human Retrovir 1990; 6:148
  41. Schonnebeck M, Krueger GRF, Braun M, Fischer M, Koch B, Ablashi DV, Balachandran N. Human herpes virus-6 infection may predispose cells for superinfection by other viruses. In Vivo 1991; 5:255-65
  42. Gosselin J, Flamand L, D'Addario M, Hiscott J, Stefanescu I, Ablashi DV, Gallo RC; Menezes J. Modulatory effects of Epstein-Barr, hepes simplex, and human Herpes-6 viral infections and coinfections on cytokine synthesis. A comparative study. J Immunol 1992; 149:181-7
  43. Flamand L, Gosselin J, Ablashi DV, D'Addario M, Hiscott J, Menezes J. Dual effect of Human herpesvirus-6 (HHV-6) on mononuclear cells: induction of IL-1a and TNFa but supression of IL-6 synthesis. J Virol 1992; 65: 5105-10
  44. M, Abts H, Li W, Schindler R, Metz H, Guenther A, von Kalle C, Schaadt M, Diamantstein T, Feller AC, Krueger GRF, Diehl V, Blankenstein T, Tesch H. Expression of interleukin-6 and interleukin-6 receptors in Hodgkin's disease. Blood 1991; 77: 2413-18
  45. Tesch H, Guenther A, Abts H, Juecker M, Klein S, Krueger GRF, Diehl V. Expression of interleukin 2Ra and interleukin 2Rb in Hodgkin's disease. Amer J Path 1993; 142:1714-20
  46. Fries KL, Miller WE, Raab-Traub N. Epstein-Barr virus latent membrane protein 1 blocks p53-mediated apoptosis through the induction of the A20 gene. J Virol 1996; 70: 8653-59
  47. Cuomo L, Trivedi P, deGrazia U, Calogero A, D'Onofrio M, Yang W, Frati L, Faggioni A, Rymo I, Ragona G. Upregulation of Epstein-Barr virus encoded latent membrane protein by human herpesvirus-6 superinfection of EBV carrying Burkitt lymphoma cells. J Med Virol 1998; 55:219-26
  48. Krueger GRF, Wagner M, Koch B, Leyssens N. Apoptosis and cell proliferation in EBV/HHV-6 positive Kikuchi's lymphadenitis and Hodkin's disease. FASEB J 1996; 10:A1010
  49. Dominguez DC, Torres ML, Antony S. Is human herpesvirus 6 linked to Kikuchi Fujimoto disease The importance of consistent molecular and serologic analysis. South Med J 2003; 96(3):226-33
  50. DeVita VT. Lymphocyte reactivity in Hodgkin's disease: a lymphocyte civil war. N Engl J Med 1973; 289: 801-2

 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618
Inicio/Home

Copyright siicsalud © 1997-2024 ISSN siicsalud: 1667-9008