Immunity parameters in adults with measles compared with healthy persons

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Abstract

Measles is a highly contagious viral infection transmitted by airborne droplets, characterized by fever, intoxication and specific rashes on the skin and mucous membranes. Despite the availability of highly effective vaccines and many years of efforts by the world medical community with active immunization of the world’s population against this infection under the auspices of WHO, measles still remains a serious problem. The aim of this work was to investigate the effect of measles infection in adults upon the wide range of lymphocyte subsets and blood cytokine profile in comparison with healthy controls.

The venous blood samples from 50 adult measles patients aged 20 to 55 years, were taken 6±1 days after the onset of skin rash, being compared with blood samples from 50 healthy adults of similar age group. The 200 μL plasma aliquotes resulting from spontaneous sedimentation of the formed elements in an Eppendorf tube were taken, frozen at -30 °C and used within 3 months for the cytokine profile assays. 15 cytokines were tested by multiplex technique (MagPix, BioRad, USA). Mononuclear cells were isolated by gradient centrifugation and immunophenotyped using four-color staining by means of equipment and reagents from BD Biosciences (USA).

In the group of measles patients, activation of innate immunity was revealed, i.e., the IL-1, IL-6, IL-23, IL-31 cytokines and TNF, which belong to early pro-inflammatory cytokines, were significantly increased. In measles patients, a significant increase in cytokines was found, suggesting active participation of epithelial cells in immune response to the measles virus. They produce danger signals (IL-25 and IL-33), inducing the development of adaptive immunity, activate their protective abilities via IL-17F production, and are involved in repair under the influence of IL-22. Some cells of adaptive immunity are infected with the measles virus and die, others actively respond to the viral infection and proliferate, thus leading to changing ratio of their subsets. Hence, the patients showed a significant decrease in T lymphocytes due to a decrease in CD4+ cells, an increased percentage of cells in “senescent” and “exhaustion” state, a significant decrease in TEMRO subpopulations, both among CD4+ and CD8+ lymphocytes, and an increase in CD8+TCM. The levels of B cell subpopulations (Bm, B1, Breg) in measles patients did not differ from healthy ones, and the level of plasmablasts was significantly increased. The level of CD4+ lymphocyte subpopulations and production of their cytokine markers varied greatly. In the patient group, a shift in the type of immune response towards Th2 and Th17 was found, activation of Tfh and Treg was detected, and increased expression of HLA-DR and CD38 activation markers was found.

In response to measles infection, there are several independent, multidirectional processes observed in the patients. On the one hand, the measles virus attacks epithelial cells of mucous membranes and skin and immunocompetent cells, exerting a cytopathic effect and leading to lymphopenia and selective decrease in various lymphocyte subsets. On the other hand, the measles virus initiates activation of both innate and adaptive immunity, thus causing production of the corresponding cytokines, expression of activation markers, and an increase in effector cell subsets. Better understanding of the immunopathogenesis of measles infection and associated immunosuppression will help us to improve vaccination outcomes against this infection and prevent measles-related mortality.

About the authors

Anna P. Toptygina

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology; Lomonosov Moscow State University

Email: toptyginaanna@rambler.ru

PhD, MD (Medicine), Leading Research Associate, Head of Laboratory of Cytokines, Professor, Department of Immunology, Faculty of Biology

Russian Federation, 125212, Moscow, Admiral Makarov str., 10; Moscow

Yuri Yu. Andreev

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology

Author for correspondence.
Email: toptyginaanna@rambler.ru

PhD Student, Laboratory of Cytokines

Russian Federation, 125212, Moscow, Admiral Makarov str., 10

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Supplementary files

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2. Figure 1. Comparison of small subsets of helpers and cytotoxic T lymphocytes in the blood of healthy and measles patients

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3. Figure 2. Subsets of naive lymphocytes and memory T cells in measles patients compared with healthy ones

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4. Figure 3. Comparison of the B cell subsets in the blood of healthy and measles patients

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Copyright (c) 2022 Toptygina A.P., Andreev Y.Y.

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