SEROLOGICAL AND MOLECULAR MARKERS OF HERPESVIRUS INFECTIONS IN THE DEBUT OF ANGIOIMMUNNOBLASTIC T-CELL LYMPHOMA


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Abstract

Background. Angioimmunoblastic T-cell lymphoma (AITL) is the rare lymphoproliferative disorder traditionally thought to be associated with EBV. This original study gives data about serological and molecular markers of herpes viruses in primary AITL patients. Materials and methods. The review includes analysis of clinical and laboratory features of 40 primary AITL patients. Peripheral blood, lymph node, bone marrow and bronco-alveolar aspirate samples were tested by ELISA, PCR and in situ hybridization. Results. Laboratory markers of the acute herpetic infection were detected in 29 (72.0%) out of 40 patients. Primary infection was detected in 8 cases: 6 - primary EBV, 1 - HCMV and 1-EBV and HCMV simultaneously. Anti-HSV 1,2 IgM were observed in 15 (37.5%) patients. EBV small non-coding RNAs (EBER) was positive in 27 (71.1%) out of 38 cases. The comparison of the detection of EBER and markers of acute EBV infection showed good correlation (p<0.001). Patients with EBER-negative lymph node samples (n=11) didn’t have any markers of acute EBV infection. Conversely, 24 of 27 (88.9%) EBER-positive cases accompanied by markers of acute EBV infection: 7 (25.9%) of them held markers of primary infection and 17 (63.0%) - reactivation. A pattern of markers of latent EBV was observed in the rest 3 (11.1%) EBER-positive cases. Conclusion. In primary AITL patients markers of herpetic infections are detected with a high frequency. EBV infection is the most frequent. The high detection rate of IgM HSM 1.2 in primary AITL patients seems to be a characteristic feature of the tumor. Obtained data proved the necessity of laboratory testing for markers of acute herpes viruses, especially in EBER-positive cases.

About the authors

Dmitriy S. Tikhomirov

National Medical Research Center of Hematology

Email: tihomirovgnc@bk.ru
MD, Ph.D, senior researcher the Laboratory of viral safety of transfusion of blood and blood components of the National Research Center for Hematology 4a, Novozykovsky proezd, 125167, Moscow, Russia

N. G Chernova

National Medical Research Center of Hematology

Email: ngchernova@mail.ru
врач-гематолог, канд. мед. наук, ФГБУ «НМИЦ гематологии» Минздрава России 4a, Novozykovsky proezd, 125167, Moscow, Russia

M. N Sinitsyna

National Medical Research Center of Hematology

Email: msini@mail.ru
врач патологоанатомического отд-ния, ФГБУ «НМИЦ гематологии» Минздрава России 4a, Novozykovsky proezd, 125167, Moscow, Russia

Yu. V Sidorova

National Medical Research Center of Hematology

Email: ouliavl@rambler.ru
ст. науч. сотр. молекулярной гематологии, канд. мед. наук, ФГБУ «НМИЦ гематологии» Минздрава России 4a, Novozykovsky proezd, 125167, Moscow, Russia

N. G Yaroslavtseva

National Medical Research Center of Hematology

Email: ngyar@yandex.ru
канд. биол. наук, ст. науч. сотр., ФГБУ «НМИЦ гематологии» Минздрава России 4a, Novozykovsky proezd, 125167, Moscow, Russia

S. M Kulikov

National Medical Research Center of Hematology

Email: kulikov.s@blood.ru
канд. технич. наук, зав. лаб. биостатистики, ФГБУ «НМИЦ гематологии» Минздрава России 4a, Novozykovsky proezd, 125167, Moscow, Russia

E. E Zvonkov

National Medical Research Center of Hematology

Email: dr.zvonkov@gmail.com
доктор мед. наук, зав. отд-нием интенсивной химиотерапии лимфом, ФГБУ «НМИЦ гематологии» Минздрава России 4a, Novozykovsky proezd, 125167, Moscow, Russia

F. P Filatov

I.I. Mechnikov Scientific Research Institute of Vaccines and Sera

Email: ffelix001@gmail.com
доктор биол. наук, вед. науч. сотр., ФГБУН «НИИ вакцин и сывороток им. И.И. Мечникова» 5a, Malyi Kazennyi pereulok, 105064, Moscow, Russia

T. A Tupoleva

National Medical Research Center of Hematology

Email: ttupoleva@mail.ru
канд. мед. наук, зав. отделом, ФГБУ «НМИЦ гематологии» Минздрава России 4a, Novozykovsky proezd, 125167, Moscow, Russia

References

  1. Swerdlow S.H., Campo E., Harris N.L., Jaffe E.S., Pileri S.A., Stein H. et al. WHO classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC; 2017: 407-410.
  2. Frizzera G., Moran E.M., Rappaport H. Angio-immunoblastic lymphadenopathy: diagnosis and clinical course. Am J Med. 1975; 59: 803-18. DOI: https://doi.org/10.1016/0002-9343(75)90466-0.
  3. Dupuis J., Boye K., Martin N., Copie-Bergman C., Plonquet A., Fabiani B. et al. Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma (AITL). A new diagnostic marker providing evidence that AITL derives from follicular helper T-cells. Am. J. Surg. Pathol. 2006; 30; 490-4.
  4. Lukes R.J., Tindle B.H. Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin’s disease. N Engl J Med. 1975; 292(1): 1-8. doi: 10.1056/NEJM197501022920101.
  5. Willenbrock K., Renné C., Gaulard P., Hansmann M.L. In angioimmunoblastic T-cell lymphoma, neoplastic T cells may be a minor cell population. A molecular single-cell and immunohistochemical study. Virchows Arch. 2005; 446(1): 15-20. https://doi.org/10.1007/s00428-004-1114-1.
  6. Weiss L.M., Jaffe E.S., Liu X.F., Chen Y.Y., Shibata D., Medeiros L.J. Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma. Blood. 1992; 79: 1789-95.
  7. de Leval L., Gisselbrecht C., Gaulard P. Advances in the understanding and management of angioimmunoblastic T-cell lymphoma. Br J Haematol. 2010; 148: 673-89. doi: 10.1111/j.1365-2141.2009.08003.x.
  8. Чернова Н.Г., Виноградова Ю.Е., Сидорова Ю.В., Капланская И.Б., Гилязитдинова Е.А., Горенкова Л.Г. и др. Длительные режимы цитостатической терапии ангиоиммунобластной Т-клеточной лимфомы. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2014; 7(1): 57-62.
  9. Баранова И. П., Курмаева А. Ю., Лесина, О. Н. Клинические особенности инфекционного мононуклеоза в зависимости от возраста и этиологии заболевания. Детские инфекции. 2010; 9(4): 25.
  10. Lome-Maldonado C., Canioni D., Hermine O., Delabesse E., Damotte D., Raffoux E. et al. Angio-immunoblastic T cell lymphoma (AILD-TL) rich in large B cells and associated with Epstein-Barr virus infection. A different subtype of AILD-TL? Leukemia. 2002; 16: 2134-41. doi: 10.1038/sj.leu.2402642.
  11. Beer T., Dorion P. Angioimmunoblastic T-Cell Lymphoma Presenting with an Acute Serologic Epstein-Barr Virus Profile. Hematol Rep. 2015; 7(2): 5893. doi: 10.4081/hr.2015.5893.
  12. Luppi M., Marasca R., Barozzi P., Artusi T., Torelli G. Frequent detection of human herpesvirus-6 sequences by polymerase chain reaction in paraffin-embedded lymph nodes from patients with angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma. Leuk Res. 1993; 17(11): 1003-11. https://doi.org/10.1016/0145-2126(93)90049-Q.
  13. Zhou Y., Attygalle A.D., Chuang S.S., Diss T., Ye H., Liu H. et al. Angioimmunoblastic T-cell lymphoma: histological progression associates with EBV and HHV6B viral load. Br J Haematol. 2007; 138(1): 44-53. doi: 10.1111/j.1365-2141.2007.06620.x.
  14. Chernova N.G., Tikhomirov D.S., Soboleva N.P., Sidorova Yu., Sinitsyna M.N., Tupoleva T.A. et. Al. Comparative analysis of serological markers of herpes viruses and hypergammaglobulinaemia in patients with Angio-immunoblastic T-cell lymphoma. Blood. 2017; 130(S1): 5180.
  15. Тихомиров Д.С., Романова Т.Ю., Игнатова Е.Н., Ярославцева Н.Г., Туполева Т.А., Гапонова Т.В. Место ПЦР в лабораторной диагностике вирусных инфекций в рутинной практике. Эпидемиология и инфекционные болезни. Актуальные вопросы. 2017; (4): 32-9.
  16. Anagnostopoulos I., Hummel M., Finn T., Korbjuhn P., Dimmler C., Gatter K. et al. Heterogeneous Epstein-Barr virus infection patterns in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type. Blood. 1992; 80: 1804-12.
  17. Macsween K.F., Johannessen I. Epstein-Barr Virus (EBV): Infectious Mononucleosis and Other Non- malignant EBV-Associated Diseases. Chapter 38 in Viral infections of humans. Epidemiology and control. 5th edition. Kaslow R.A., Stanberry L.R., Le Duc J. W. 2014. 867-96.
  18. Longnecker R. M., Kieff E., Cohen J. I. Epstein-Barr Virus. In: Knipe D.M., Howley P.M., Griffin D.E., Lamb R.A., Martin M.A., Roizman B., eds. Fields virology. Chapter 61. Philadelphia: Lippincott Williams Wilkins; 2013. vol. 2: 1898-1959.
  19. Гурцевич В.Э. Роль вируса Эпштейна-Барр в онкогематологических заболеваниях человека. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2010; 3(3): 222-34.
  20. Gru A.A., Haverkos B.H., Freud A.G., Hastings J., Nowacki N.B., Barrionuevo C. et al. The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment. Curr Hematol Malig Rep. 2015; 10(4): 456-67. doi: 10.1007/s11899-015-0292-z.
  21. Чернова Н.Г., Тихомиров Д.С., Гаранжа Т.А., Клясова Г.А., Рощина Л.С., Грачева А.Н. и др. Вирусные поражения слизистых оболочек органов желудочно-кишечного тракта у больных лимфомами. Терапевтический архив. 2014; 86(7): 93-6.
  22. Ishii Y., Itabashi M., Numata A., Yamamoto W., Motohashi K., Hagihara M. et al. Cytomegalovirus pneumonia after anti-CC-chemokine receptor 4 monoclonal antibody (mogamulizumab) therapy in an angioimmunoblastic T-cell lymphoma patient. Internal Medicine. 2016; 55(6): 673-75. https://doi.org/10.2169/internalmedicine.55.5644.
  23. Mocarski E.S., Shenk Jr.T., Griffiths P.D., Pass R.F. Cytomegaloviruses. In: Knipe D.M., Howley P.M., Griffin D.E., Lamb R.A., Martin M.A., Roizman B., eds. Fields virology. Chapter 62. Philadelphia: Lippincott Williams Wilkins; 2013. vol. 2: 1960-2014.
  24. Roizman B., Knipe D.M., Whitley R.J. Herpes Simplex Viruses. Chapter 60 in Fields Virology 6th edition. Knipe D.M., Howley P.M. 2013.
  25. Тихомиров Д.С., Гаранжа Т.А., Туполева Т.А., Троицкая В.В., Галстян Г.М., Филатов Ф.П. Факторы, влияющие на частоту возникновения вирусных пневмоний у онкогематологических больных. Гематология и трансфузиология. 2016; 61(1): 37-42,
  26. Guerrero M.D., Swenson K.K. Herpes simplex virus-related oral mucositis in patients with lymphoma. Oncology nursing forum. 2014; 41(3): 327-30. doi: 10.1188/14.ONF.327-330.
  27. Moldovan B., Mentha G., Majno P., Berney T., Morard I., Giostra E. et al. Demographics and outcomes of severe herpes simplex virus hepatitis: a registry-based study. Journal of hepatology. 2011; 55(6): 1222-6. doi: 10.1016/j.jhep.2011.02.029.

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