The effect of active and latent Herpes Simplex Virus-1,2 (HSV-1,2) infections on peripheral blood lymphocyte subpopulation composition in patients with inflammatory diseases of the anterior eye segment

Herpes simplex virus-1 (HSV-1), Herpes simplex virus-2 (HSV-2) cause lifelong infections with two-phase cycle: productive lytic and latent phase. The aim of this research work was to study the effect of HSV-1, HSV-2 on immune status of patients in latent and lytic phases of infection. Materials and methods. 99 people with anterior uveitis, corneal ulcers, episcleritis, scleritis. IgG-antibodies to late and early antigens (IE antibodies — markers of latent infection reactivation) of HSV-1, HSV-2, and CMV (comparison virus) were determined in blood serum by ELISA. Immune status was assessed in whole blood by flow cytometry (BD FACS Canto II, USA): percentage and absolute count of lymphocytes (CD45⁺), T lymphocytes (CD3⁺), cytotoxic T lymphocytes (CD3⁺CD8⁺), T helper cells (CD3⁺CD4⁺), double-positive lymphocytes (CD3⁺CD4⁺CD8⁺), natural killer cells (CD3^–CD16⁺CD56⁺), B lymphocytes (CD19⁺), CD4⁺/CD8⁺ ratio. Statistical analysis: StatTech v.4.7.2 (Russia). Results. 86 out of 99 patients were infected with HSV-1,2, 84 out of 98 — with CMV. Reactivation of HSV-1 detected in 47 patients, HSV-2 — 13, CMV — 17. 13 patients were seronegative for HSV-1,2, and 14 — for CMV. Group 1 included infected with HSV-1,2 and/or CMV patients; group 2 included not infected patients. In group 1, subgroups with latent and lytic phases were identified. Immune status in patients with latent HSV-1,2 infection was mainly the same as in lytic phase. During HSV-1 reactivation, proportion of CD3⁺CD8⁺ decreased, while proportion of CD3⁺CD4⁺, CD3^–CD16⁺CD56⁺ absolute count, CD4⁺/CD8⁺ ratio increased (p < 0.05). In HSV-2 reactivation and latent HSV-1,2 infection, in contrast to HSV-1 reactivation, there was an additional increase in CD3⁺CD4⁺ (%) and CD45⁺. Unlike HSV-1 and HSV-2, in comparison group patients proportion of CD3⁺CD8⁺ (497.95±118.01) decreased significantly compared to latent CMV infection (620.38±326.38; p = 0.026). Conclusion. Unidirectional changes in immune status of patients with latent and lytic phases of HSV-1,2 infection are likely associated with low levels of viral reactivation and weak humoral response in some. Therefore, patients with “false-negative” results of early antibody testing could have been included in the group with latent HSV-1,2 infection. Apparently, a single test for HSV-1,2 reactivation markers is insufficient to rule out subclinical infection activity. Undiagnosed HHV reactivation in patients with inflammatory ophthalmopathology may be prognostically unfavorable.