Determination of Some Immunological Features of HHV-6-Mediated Infectious Mononucleosis in Children by the Method of Discriminatory Analysis

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.

Molecular Markers of EBV- and HHV6-Associated Mononucleosis

“…Epstein-Barr virus (EBV, Human gammaherpesvirus 4) and human herpesvirus type 6 (HHV6, Human betaherpesvirus 6) are members of the Herpesviridae family that cause infectious mononucleosis (IM). Both viruses have tropism for various immunocompetent cells, can change the number of these cells in the blood [1], and contribute to the development of lymphoproliferative diseases [2][3][4]. To date, there are no effective means of targeted therapy for the disease.…”