DETERMINATION OF SOME IMMUNOLOGICAL FEATURES OF HHV-6-MEDIATED INFECTIOUS MONONUCLEOSIS IN CHILDREN BY THE METHOD OF DISCRIMINATORY ANALYSIS

Cover Page


Cite item

Full Text

Abstract

Human herpesvirus type 6 (HHV-6) is a lymphotropic virus that is an etiological agent of infectious mononucleosis (IM) in children. HHV-6- mediated infectious mononucleosis (HHV-6M) does not have clearly  defined clinical features. Nowadays immunopathogenetic aspects of  this disease have not been fully understood. The purpose of this  work was to study the characteristics of the quantitative composition  of populations of immunocompetent cells of peripheral  blood in children with HHV-6M. The material for the study was  samples of peripheral blood from children with “infectious  mononucleosis” diagnosis and from virtually healthy children.  Depending on the etiologic cause of the disease, children with IM  were divided into three groups: HHV-6M, IM of other etiology and  mixed infection (combination of HHV-6 and Epstein–Barr virus  and/or Cytomegalovirus). Virtually healthy children formed the  fourth group. In blood samples, the absolute content of the following populations of immunocompetent cells was determined by the  method of flow cytometry: the total population of T-lymphocytes, T- helpers, cytotoxic T-lymphocytes, double positive T-lymphocytes  (CD4+CD8+), NK cells and B-lymphocytes. Discriminant analysis  was carried out: based on the obtained data on the population  composition of blood cells we constructed a model of a child’s  attribution to one of the four groups analyzed in pairs. We used the  method of machine learning — the algorithm of gradient boosting  over decision trees. It was determined whether it is possible to  classify patients on the basis of the studied indicators and which  combination of indicators is optimal for classification. As a result of  the study it was possible to classify the following pairs of groups:  healthy children — children with HHV- 6M, healthy children —  children with IM of other etiology, children with HHV-6M — children  with IM of other etiology. When solving the problem of classifying  children from group with mixed infection and from any other group,  it was not possible to find a model of satisfactory quality. In  comparison with virtually healthy children, children with HHV-6M were characterized by an increased content of the total  population of T-lymphocytes and cytotoxic T-cells, as well as by a  reduced content of doub le-positive T-lymphocytes. Compared with  children with IM of other etiology, children with HHV-6M were  characterized by an increased content of cytotoxic T-lymphocytes, T- helpers, B-lymphocytes and a reduced number of double-positive T  cells. Our results indicate that HHV-6-mediated infectious  mononucleosis causes changes in the quantitative composition of  certain populations of immunocompetent cells of peripheral blood,  different from those of other etiology, in children.

About the authors

E. N. Filatova

Blokhina Scientific Research Institute of Epidemiology and Microbiology of Nizhny Novgorod

Author for correspondence.
Email: filatova@nniiem.ru

PhD (Biology), Senior Researcher, Laboratory of Molecular  Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation

603950, Russian Federation, Nizhny Novgorod, Malaya Yamskaya str., 71

Phone: +7 (831) 469-79-46 (office). Fax: +7 (831) 469-79-20

 

Россия

L. A. Solntsev

Blokhina Scientific Research Institute of Epidemiology and Microbiology of Nizhny Novgorod

Email: fake@neicon.ru

PhD (Biology), Head of the Laboratory of GISTechnology and  Bioinformatics, Blokhina Research Institute of Epidemiology  and Microbiology, Nizhny Novgorod, Russian Federation

Россия

N. B. Presnyakova

Blokhina Scientific Research Institute of Epidemiology and Microbiology of Nizhny Novgorod

Email: fake@neicon.ru

Researcher, Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation

Россия

E. A. Kulova

Nizhny Novgorod State Medical Academy

Email: fake@neicon.ru

PhD (Medicine), Assistant of the Department of Children  Infections, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation

Россия

O. V. Utkin

Blokhina Scientific Research Institute of Epidemiology and Microbiology of Nizhny Novgorod

Nizhny Novgorod State Medical Academy

Email: fake@neicon.ru

PhD (Biology), Head of the Laboratory of Molecular Biology  and Biotechnology, Blokhina Research Institute of  Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation; Associate Professor, Department of  Microbiology and Immunology, Privolzhsky Research Medical  University, Nizhny Novgorod, Russian Federation

Россия

References

  1. Новосад Е.В., Шамшева О.В., Львов Н.Д., Мельниченко А.В., Егорова Н.Ю., Михайловская Г.В., Никитина А.А., Зоненштайн Т.П. Инфекционный мононуклеоз, ассоциированный с вирусом герпеса 6 типа // Детские инфекции. 2008. Т. 7, № 1. С. 36– 38. [Novosad E.V., Shamsheva O.V., Lvov N.D., Melnichenko A.V., Yegorova N.Yu., Mikhaylovskaja G.V., Nikitina A.A., Zonenshayn T.P. Infectious mononucleosis, associated with herpes virus type 6. Detskie infektsii = Children’s Infections, 2008, vol. 7, no. 1, pp. 36–38. (In Russ.)]
  2. Филатова Е.Н., Уткин О.В. Современные подходы к моделированию герпесвирусной инфекции // МедиАль. 2014. № 2 (12). С. 172–197. [Filatova E.N., Utkin O.V. Modern approaches to the modeling of herpesvirus infection. MediAl’ = MediAl, 2014, no. 2 (12), pp. 172–197. (In Russ.)]
  3. Ablashi D.V., Lusso P., Hung C.L., Salahuddin S.Z., Josephs S.F., Llana T., Kramarsky B., Biberfeld P., Markham P.D., Gallo R.C. Utilization of human hematopoietic cell lines for the propagation and characterization of HBLV (human herpesvirus 6). Int. J. Cancer, 1989, vol. 42, iss. 5, pp. 787–791. doi: 10.1002/ijc.2910420526
  4. Ablashi D.V., Marsh S., Kaplan M., Whitman J.E., Pearson G.R. HHV-6 infection in HIV-infected asymptomatic and AIDS patients. Intervirology, 1998, vol. 41, no. 1, pp. 1–9. doi: 10.1159/000024909
  5. Arvin A., Campadelli-Fiume G., Mocarski E., Moore P.S., Roizman B., Whitley R., Yamanishi K. Human herpesviruses: biology, therapy and immunoprophylaxis. Cambridge: Cambridge University Press, 2007, 1408 p.
  6. Dagna L., Pritchett J.C., Lusso P. Immunomodulation and immunosuppression by human herpesvirus 6A and 6B. Future Virol., 2013, vol. 8, no. 3, pp. 273–287. doi: 10.2217/fvl.13.7
  7. Dewhurst S., McIntyre K., Schnabel K., Hall C.B. Human herpesvirus 6 (HHV-6) variant B accounts for the majority of symptomatic primary HHV-6 infections in a population of U.S. infants. J. Clin. Microbiol., 1993, vol. 31, no. 2, pp. 416–418.
  8. Flamand L., Gosselin J., Stefanescu I., Ablashi D., Menezes J. Immunosuppressive effect of human herpesvirus 6 on T-cell functions: suppression of interleukin-2 synthesis and cell proliferation. Blood, 1995, vol. 85, iss. 5, pp. 1263–1271.
  9. Lusso P., De Maria A., Malnati M., Lori F., DeRocco S.E., Baseler M., Gallo R.C. Induction of CD4 and susceptibi lity to HIV-1 infection in human CD8+ T lymphocytes by human herpesvirus 6. Nature, 1991, vol. 349, no. 6309, pp. 533–535. doi: 10.1038/349533a0
  10. Overgaard N.H., Jung J.-W., Steptoe R.J., Wells J.W. CD4+/CD8+ double-positive T cells: more than just a developmental stage? J. Leukoc. Biol., 2015, vol. 97, iss. 1, pp. 31–38. doi: 10.1189/jlb.1RU0814-382
  11. Pedregosa F., Varoquaux G., Gramfort A., Michel V., Thirion B., Grisel O., Blondel M., Prettenhofer P., Weiss R., Dubourg V., Vanderplas J., Passos A., Cournapeau D., Brucher M., Perrot M., Duchesnay E. Scikit-learn: machine learning in Python. J. Mach. Learn. Res., 2011, vol. 12, pp. 2825–2830.
  12. Soldan S.S., Berti R., Salem N., Secchiero P., Flamand L., Calabresi P.A., Brennan M.B., Maloni H.W., McFarland H.F., Lin H.C., Patnaik M., Jacobson S. Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA. Nat. Med., 1997, vol. 3, no. 12, pp. 1394–1397.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2018 Filatova E.N., Solntsev L.A., Presnyakova N.B., Kulova E.A., Utkin O.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies