PECULIARITIES OF EFFECTOR LYMPHOCYTES SUBPOPULATIONS IN PATIENTS WITH UVEAL MELANOMA DURING ACTIVATION AND CHRONIC PROGRESS OF HERPESVIRAL INFECTION

The immune response to any antigen includes the induction of effector and regulatory T lymphocytes. In tumors, an imbalance in the subpopulation of lymphocytes is noted. Ophthalmotropic pathogens of herpes virus infections play a role in the etiopathogenesis of some oncological processes in the tissues of the eye. Their “cancer modulating” role is to regulate the functions of immunocompetent cells by viruses and reprogram it in the direction of greater progression of tumor growth. The aim of our study was a comparative analysis of the content of effector subpopulations of blood lymphocytes in patients with uveal melanoma during activation and the chronic course of herpes virus infection. The study involved 141 people: with uveal melanoma 70 patients, with corneal ulcers and involvement of the uveal tract - 38 patients and 33 healthy donors. Immunophenotyping was performed by flow laser cytofluorimetry using a monoclonal antibody system to differentiate lymphocyte subpopulations. IgM and IgG antibodies to herpes virus infections were determined in an enzyme-linked immunosorbent assay (ELISA) on an automatic ELISA analyzer "Lazurite" (USA) with diagnostic kits of CJSC Vector-Best (Koltsovo). The results of the study showed that the absolute number of blood lymphocytes (CD45 +) in patients with uveal melanoma, regardless of the presence of active or chronic herpes virus infection, did not differ from the values in healthy donors. In patients with corneal ulcers involving the uveal tract, an increase was noted. A decrease in the relative and absolute content of T cells (CD3+) was revealed in patients with uveal melanoma during activation and the chronic course of herpes virus infection. An increase in the absolute content of CD3 + was noted in patients with active and chronic herpesvirus infection in patients with inflammatory lesions of the eye. There was no difference in the relative and absolute contents of the subpopulation of CD3 + CD4 + helpers / inducers upon activation of herpes virus infections in tumor. With corneal ulcers - a significant increase in the absolute content of CD3 + CD4 + helpers / inducers with active and chronic infection. In chronic herpes virus infection, an increase in the relative and absolute number of cytotoxic T-lymphocytes (CD3 + CD8 +) with uveal melanoma was revealed. With active infection, a decrease in the relative number of T-lymphocytes (CD3 + CD8 +) in the tumor was noted. With corneal ulcers involving the uveal tract, an increase in the absolute content during activation and chronic infection and a decrease in the relative content compared to the norm were determined. When analyzing the “double positive” T cells in a tumor, an increase in relative and absolute indices was observed in chronic and active infection with herpes viruses. The same trends were observed with inflammatory eye diseases. Analysis of the content of B-lymphocytes (CD19 +) in blood with melanoma showed an increase in the absolute number during activation and the chronic course of herpes virus infection. When analyzing the indicators of the absolute and relative content of B-lymphocytes (CD19 +) with inflammation of the membranes of the eyes, their increase was revealed regardless of activation or chronic infection. The relative number of natural killers (CD16 + CD56 +) of blood with uveal melanoma increased with infection activation. In inflammatory eye diseases, a decrease in the relative content of natural killers (CD16 + CD56 +) was found in chronic infection and active herpes virus infection. With melanoma, no changes in the index of the ratio CD4 + / CD8 + were detected, with ulcerative lesions of the cornea involving the uveal tract, its increase was noted in acute and chronic infections with herpes virus infections. (p <0.05). Thus, our own studies suggest a deep suppression of the immune system of the body of patients with uveal melanoma, which does not allow the activation of antiviral protection. Tumor causes multidirectional shifts in the relative and absolute content of lymphocytes during activation and chronic infection with herpes virus infections. The results obtained are important for the development of personalized approaches to the prognosis and treatment of patients with uveal melanoma.

Effectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres

Background: Oral cladribine has been approved for the treatment of relapsing multiple sclerosis (MS) yet real-world evidence regarding its effectiveness and safety remains scarce. Objective: To evaluate efficacy and safety outcomes of MS patients following induction of cladribine. Methods: We evaluated our prospective cohort of cladribine-treated MS patients from two tertiary centres in Germany. Relapses, disability worsening and occurrence of new or enlarging T2-hyperintense magnetic resonance imaging (MRI) lesions were assessed as well as lymphocyte counts and herpes virus infections. Results: Among 270 patients treated with cladribine, we observed a profound reduction of both relapses and new or enlarging MRI lesions. Treatment appeared more efficacious, especially in patients without previous therapy or following platform substances. Patients switching from natalizumab were prone to re-emerging disease activity. Among patients following dimethyl fumarate pre-treatment, severe lymphopenia was common and associated with increased rates of herpes virus manifestations. Conclusion: Overall, we observed an efficacy and safety profile of cladribine consistent with data from the phase 3 clinical trial. However, patients switching from natalizumab experienced suboptimal disease control beyond rebound activity following cessation of natalizumab. Furthermore, dimethyl fumarate pre-treatment was associated with a profound risk of developing severe lymphopenia and subsequent herpes virus infections.

Prolonged subfebrile condition in children. Possible causes, diagnostics

Prolonged subfebrile condition (PSC) is a complex diagnostic and therapeutic problem caused by a wide variety of reasons, which often require a wide and expensive examination, consultations of various specialists, and repeated hospitalizations. Most often, PSC is associated with infections, some non-infectious diseases (predominantly connective tissue) and growths. To infectious causes of DS include: acute respiratory viral infections, herpes virus infections, toxoplasmosis, chlamydia, borreliosis, bartonellosis, etc. Separately, “psychogenic fevers”, subfebrile condition associated with taking drugs, and artifical subfebrile condition are distinguished. The condition of the children, as a rule, is benign and in most cases goes away on their own within 6-24 months.

Immunopathogenetically reasonable program effectiveness of systemic and local interferonotherapy in immunocompromised young children

Relevance. In recent years, there has been a steady increase in the incidence of children morbidity, in the structure of which infectious pathology occupies a leading position. The development of minimal persistent inflammation of the upper respiratory tract mucosa is the basis for the persistence of microflora, the entrance gate for allergens and irritants, and creates conditions for the timing of the inflammation. The aim of the study: based on the study of the features of the immune system and interferon system in immunocompromised children of early age suffering from co-infections: return ARVI associated with atypical chronic herpes virus infections, to develop a new program of local and systemic interferon therapy and evaluate its effectiveness. Materials and methods: We observed 30 children aged 1-4 years, 16 boys and 14 girls suffering from recurrent ARVI associated with various atypical chronic active herpes virus infections (ACHA-HVI) (HSV I/II, EBV, CMV, HHV VI). The comparison group was 20 conditionally healthy children, comparable by sex and age. We used clinical and immunological methods: ELISA, PCR, cytofluorimetry. Results: A clinical and anamnestic investigation showed that young children had clinical features of immunocomprometization: a high rate of recurrent ARVI of 10-15 or more episodes per year, and the duration of these episodes ranged from 7 to 12 days, while in 100 % of cases there were recurrent monoand/or mixed ACHA-HVI. A study of the state of the immune system and the interferon system showed that children of the study group were deficient in T cytotoxic lymphocytes, natural killer cells, serum IFN, serum IgA, and various disorders of neutrophil granulocytes (NG). A new immunopathogenetically based program of local and systemic therapy with recombinant IFN2b in combination with antioxidants has been developed. This program demonstrated a high clinical-immunological effectiveness, providing in a significant reduction of ARVI episode rates, a reduction in the duration of IRVI, as well as the number of complicated ARVI, a decrease in the replicative activity of herpes viruses in a field of restoration of the interferon system, a significant improvement of antiviral and antibacterial immune response. Conclusions: A new immunopathogenetically based program of systemic and local IFNtherapy for immunocompromised young children has been created. The high clinical-immunological effectiveness and immunoprophylactic orientation of the developed local and systemic program of interferonotherapy have been demonstrated.

Clinical manifestations of infectious mononucleosis in primary or reactivated herpes virus infection

Based on the analysis of foreign and domestic literature, the article presents the features of infectious mononucleosis caused by the main pathogens from the Herpesviridae family, course of the disease at various phases of the infectious process. The article identifies clinical and laboratory manifestations characteristic of each pathogen. The authors discuss the issues related to the lack of the unified terminology for describing chronic herpes virus infection. The article discusses the causes of persistent herpes virus infections, risk factors for the adverse course and outcome of herpes virus infections.