Immune disorders and their correction in patients with herpes infection of the oropharynx

Abstract

Recurrent herpes infection of the oropharynx caused by herpes simplex virus type I and II occupies an important place among the infectious diseases of the oral cavity. The mechanisms which lead to the development of recurrence of the disease are studied insufficiently, and this limits the clinical possibilities of prophylactics. The frequency of the manifestations of herpetic infection and their intensity depend on the state of the immune system, in particular, the nature and level of pathogenic disorders of immune response. The immunotherapy requires a personalized approach taking into account the variability of “sensitivity” of immune index of the patient for potential therapeutic effects. The aim of the study was to justify the treatment of immune disorders and timeous prevention of recurrence, and also complications that occur when infection activates during the long-term viral persistence, based on definition of the characteristics of immune disorders in patients with moderate and high recurrence rate of the disease. Materials and methods. The study involved 86 patients aged 18 to 49 years with herpesviral gingivostomatitis and pharyngotonsillitis and herpetic vesicular dermatitis. The control group consisted of 19 healthy people of comparable age. Patients with recurrent HSV infection were divided into two groups. Group I was formed of patients with moderate rates of relapse less than 4 times per year (n = 51), and group II represented patients with high rates of relapse not less than 4 times a year (n=35). Lymphocyte subsets were defined by fluorescent microscopy method using FITC-labeled monoclonal antibodies against surface antigens CD3, CD4, CD8, CD16, CD22. Evaluation of functional lymphocyte reactivity was performed by setting 5 mg/ml PHA-stimulated RBTL. Phagocytic activity was defined by latex method. The NBT-test was used to evaluate the metabolic capacity of phagocytes. The CIC in serum were defined by method of selective 3.5% PEG precipitation of antigen complexes. Complementary activity of blood serum was determined by 50% hemolysis. The content of IFN-α and IFN-γ in supernatants was determined by ELISA after 24 hours of PBMC incubation. Results and discussion. The level of immunodeficiency disorders expression by herpes infection depended on the frequency of relapses during the year. A decrease of white blood cells number and relative content of lymphocytes of about 1.6 times as compared to the control group was observed in patients with a high relapse rate of recurrent HSV. Herewith, the relative content of CD8 + lymphocytes was 1.4 times lower than the control and 1.5 times lower than the same index in patients with moderate recurrent HSV relapse rate, and reduction of RBTL stimulation index was expressed stronger as compared with the control group. Levels of serum IgA and IgG were increased 2.1 times and 1.7 times respectively relative to the control group. Concentration of CIC in serum of patients in both groups exceeded the control which points to the failure of elimination function. A significant decrease in phagocytic activity in both groups in patients with recurrent HSV was more expressed in the group with high frequency of relapses. Also the decrease metabolic reserves were found in both groups of patients which points to the phagocytic function disorder. Elevated level of B-lymphocytes and increased level of immunoglobulins points to the activation of humoral immunity. Activity of complement in patients with recurrent HSV was significantly higher than controls (1.4 times) in the group with high frequency of relapses. Expressed deficiency of IFN-α compared with controls and patients with moderate frequency of relapses were observed in the group of patients with a high relapse rate. The level of spontaneous production of IFN-α was elevated 1.6 times compared to control in patients with moderate frequency of recurrent HSV relapses, and the level of spontaneous production of IFN-γ was elevated 1.3 times compared to control group. In our previous studies we have determined that the content of perforin-positive cytotoxic lymphocytes in patients with a high frequency of disease relapses was reduced 2 times relative to healthy donors. It was shown that HSV-inactivated vaccine was able to elevate the content of perforin-positive cytotoxic lymphocytes in patients with moderate and high recurrence rate; herewith the largest index of influence of HSV-antigen was defined in patients with a high frequency of relapses. HSV-induced production of IFN-α increased 3 times in patients with moderate frequency of relapses and it had no significant difference from the control group, and in patients with a high relapse rate - 2.3 times. Reserve ability to synthesize IFN-γ in patients with moderate frequency of HSV relapses remained at the level of index of almost healthy donors, while the expressed reduction of stimulating action of HSV antigen was observed in patients with a high relapse rate. We have previously shown that the high recurrence rate of herpes infection accompanies by reduction of levels of TNF-α, by increase of spontaneous and induced production of IL-10 (in 76% patients), IL-12 and IL-1β by monocyte cells (in 85% of cases). Herewith 67% of patients with a high frequency of disease relapses had an imbalance of IL-12p70/IL-12p40, and 43% of patients had increased production of IL-1 receptor antagonist.It was determined that incubation of PBMCs with the addition of recombinant IFN-α causes a significant increase of the production of IFN-γ in patients with moderate relapse rate and also in the control group (stimulation index 1.3). The level of interferon-induced IFN-γ had no significant difference from the basal level in patients with a high relapse rate. Regulatory effect of IFN-α manifested also as increase of production of IL-1β, herewith the increase of the ratio IL-1β/IL-1RA was noted in patients with a high relapse rate. Stimulation of IFN-α in patients with a high relapse rate leads to 1.4 times increase of induced production of IL-10 by cells of monocyte fractions of MNC. The influence of IFN-α on the relative content of perforin-positive lymphocytes in patients with recurrence HSV was less expressed as compared to HSV-vaccine. So the stimulation index in patients with moderate relapse rate was 1.4, while patients with high relapse rate had stimulation index 1.2. Thereby, the choice of immunotherapeutic strategy of treatment of recurrent herpes infection of the oropharynx requires the immunological test to clarify the HSV pathogenesis type.