Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naïve Boy Is Associated With a Novel SH2D1A Mutation

X-linked lymphoproliferative disease (XLP1) is a combined immunodeficiency characterized by severe immune dysregulation caused by mutations in the SH2D1A/SAP gene. Loss or dysfunction of SH2D1A is associated with the inability in clearing Epstein-Barr-Virus (EBV) infections. Clinical manifestation is diverse and ranges from life-threatening hemophagocytic lymphohistiocytosis (HLH) and fulminant infectious mononucleosis (FIM) to lymphoma and antibody deficiency. Rare manifestations include aplastic anemia, chronic gastritis and vasculitis. Herein, we describe the case of a previously healthy eight-year old boy diagnosed with XLP1 presenting with acute non-EBV acute meningoencephalitis with thrombotic occlusive vasculopathy. The patient developed multiple cerebral aneurysms leading to repeated intracerebral hemorrhage and severe cerebral damage. Immunological examination was initiated after development of a susceptibility to infections with recurrent bronchitis and one episode of severe pneumonia and showed antibody deficiency with pronounced IgG1-3-4 subclass deficiency. We could identify a novel hemizygous SH2D1A point mutation affecting the start codon. Basal levels of SAP protein seemed to be detectable in CD8+ and CD4+ T- and CD56+ NK-cells of the patient what indicated an incomplete absence of SAP. In conclusion, we could demonstrate a novel SH2D1A mutation leading to deficient SAP protein expression and a rare clinical phenotype of non-EBV associated acute meningoencephalitis with thrombotic occlusive vasculopathy.

Method for predicting the course of peritonsillar abscess in patients with exacerbation of chronic tonsillitis

Objectives clinical and laboratory examination of patients with acute tonsillitis for early diagnosis and prognosis of peritonsillar abscess. Material and methods. The study included 101 patient with lacunar tonsillitis complicated by peritonsillar abscess and 64 donors (control group). Immunological studies were performed according to WHO recommendations, on the basis of the immunological department of the EMB Research Institute and the immunological laboratory of the SamSMU. Results. Immunological examination of patients with abscess showed an increase in: neutrophil phagocytic activity, CD4+/CD8+, the number of cells expressing HLA-DR+ markers, complement activity, IgA, IgM, IgG plasma concentration, fibronectin level, pro-inflammatory cytokines IL-8, IL-1, IL-1 and a decrease in: the level of TNF-, myeloperoxidase activity, number of cells containing CD4+, CD8+, CD16+, CD20+, CD25+ markers. High correlation was registered between total lymphocytes and CD3+ and CD4+ cells (p 0.01); between CD3+ and CD4+ markers (p 0.01); as well as high correlation of IL-1 levels with IL-8 and IL-1 (p 0.01). Cluster analysis revealed different types of immune homeostasis. The first type (cluster) had high values of leukocytes (total), lymphocytes (total), cells with CD3+, CD4+, CD8+, CD16+, CD20+, CD95+ and HLA-DR+ markers; the second type (cluster) was characterized by significantly lower levels of these immune status indicators. 41 patient had the first type of immune response, with an explicit clinical picture and rapid formation of an abscess. The second type of immune response was registered in 60 patients having a torpid course of the disease with delayed development of abscess. Further, to assess the type of immune reactions, it is necessary to substitute the values of indicators into the model and calculate the integral coefficient of the body's reaction (ICTROI and ICTROII).

Comparative Assessment of the Dynamics of Immunological Reactivity in Patients With Postoperative Ventral Hernia

Postoperative Ventral Hernias to this day remain one of the main pathologies of planned and urgent surgical interventions. The purpose of the study is to study the immune response in patients with postoperative ventral hernias who underwent auto and alloplastic hernioplasty methods. The study included 40 patients diagnosed with postoperative ventral hernia, including 25 men (62.25%) and 15 women (37.5%). In men, the average age was 45.6±2.3 years, and in women 57.2±3.2 years. Patients are divided into 2 groups. Group I are patients who underwent autoplastic methods and group II patients who underwent alloplastic hernioplasty methods. The complex of immunological examination included the determination of a subpopulation of lymphocytes with CD3, CD4, CD8, CD20 receptors, interleukin 6, interleukin 10 and immunoglobulins A, M, G. Immunological examination of blood parameters in patients with postoperative ventral hernias revealed the following changes. There is an upward trend in all indicators. In group I, the leukocyte level was increased by +0.2±0.01, and in group II, the indicators were within the normal range. The level of monocytes in patients who underwent alloplasty increased by +1.5±0.2. There was an increase in the concentration of T and B lymphocytes with GD3, CD4, CD8, CD20 receptors on the 7th day after surgery in patients of the first group was +1.85±0.3, +1.6±0.4, +1.6±0.1, +1.5±0.2. And in patients of the second group, the initial level of indicators was lower and increased by +1.2±0.1, +1.4±0.2, +1.67±0.65, +1.03±0.45. The level of IL6 and IL 10 in the postoperative period increased in patients of the first group by +1.55±0.2 and +1±0.9, in the second group it was IL 6 +0.9±1.2, IL 10 +0.8±1.2. The study shows that the indicators of the humoral cell type tended to increase, which shows the result. Conclusions. Patients with postoperative ventral hernias who have undergone autoplastic and alloplastic hernioplasty methods in dynamics, the immunological reactivity indicators significantly increase on the 7th day, in comparison with the initial blood parameters. Namely, in patients who have undergone autoplastic methods of hernioplasty. The use of conventional suture materials in autogernioplasty increases the risk of developing an inflammatory process in the early and long-term postoperative period, in contrast to the use of polypropylene mesh prostheses.

Study of risk factors for the osteoporosis development in rheumatoid arthritis in real clinical practice

Introduction. Osteoporosis is a common complication of rheumatoid arthritis. Its development is associated with the mechanisms underlying in the progression of autoimmune inflammatory diseases and therapeutic approaches used for them. The study of risk factors for osteoporosis can contribute to the clarification of its pathogenesis components, as well as the development of new methods for prevention, diagnosis and treatment of this condition.Aim. To study the role of anamnestic, clinical and laboratory factors for secondary osteoporosis in women with rheumatoid arthritis.Materials and methods. 102 women with rheumatoid arthritis were enrolled in our study. Exclusion criterias were type 2 diabetes mellitus, hepatic cirrhosis, hepatocarcinoma and level of alanine aminotransferase ≥ than 3 upper limit ofnormal. The cumulative dose, duration and daily dose of glucocorticoids (GC) were determined by patient intake. All patients undergone standard clinical and immunological examination. Serum fetuin-A, 25-hydroxycalciferol, C-telopeptide of collagen I type, N-terminal propeptide of collagen I type levels were determined using ELISA. X-ray of afflicted joints and dual-energy x-ray absorptiometry were performed. Statistical analysis was performed using conventional methods. Forced data entry was used to perform multiple logistic regression. Hereinafter data is presented as odds ratio (OR) and 95% confirmation intervals (CI).Results. OR for osteoporosis were higher in women of age ≥ 58.5 years (OR 1,07 (1.02–1.12)), body mass index (BMI) ≤ 27 kg/m2 (OR 1.1 (1.01–1.2)), cumulative dose of GC ≥ 7.6 g (OR 1.09 (1.02–1.17), serum fetuin-A levels ≤ 660 μg/ml (OR 1,05 (1,01–1,09) and if the duration of GC intake is more than 3 months (hereinafter if dose of glucocorticoids is ≥ 5 mg for prednisolone daily) (OR 12.3 (4.12–36.5). Adjusted OR for osteoporosis were higher in women of age ≥ 58.5 years old (adjOR 1.08 (1.01–1.16), serum fetuin-A levels ≤ 660 μg/ml (adjOR 1.08 (1.01–1.15) andif the duration of GC intake is ≥ than 3 months (adjOR 12.1 (1.44–102.3).Conclusions. Women with RA of ≥ than 58.5 years old, duration of GCs intake more than 3 months and serum fetuin-A levels ≤ than 660 μg/ml had higher odds for osteoporosis.These are independent factors for osteoporosis in women with rheumatoid arthritis, whichshould be used in patient’s management.

Hormone therapy affecting interferon defense in children with infectious mononucleosis

23 children diagnosed with acute infectious mononucleosis were hospitalized and examined after a short prednisolone treatment course. Related interferon status during infection was compared with that in 38 patients with acute infectious mononucleosis receiving no hormone therapy. Interferon status was investigated by Ershov method, allowing to estimate amount of interferon in the blood serum samples or patient blood cell culture by assessing interferon biological activity. Along with measuring IFNα or IFNγ biological activity, their level was quantified by using enzyme immunoassay. Immunological examination conducted on the next day after the end of hormone therapy revealed sharply decreased potential of patient blood cells to produce both IFNα and IFNγ. The multiplicity of IFNα and IFNγ titer reduction in various patients varied by 4–5 and 3–4-fold, respectively. The concentration of IFNα, determined by ELISA, decreased by 4–6-fold, whereas for IFNγ — by 1.5–2-fold. A follow-up examination 1 month after discharge from the clinic showed that mean IFNα titer in children aged 3–6 years and treated with prednisolone was significantly reduced compared to the baseline, whereas most patients receiving no hormone therapy had normal IFNα production. The change in the level of IFNα 1 month after hormone therapy in 7–14-year age group was similar. IFNγ production quickly recovered, and 1 month after discharge from the clinic, its concentration in culture supernatants from patients reached 10–15 ng/ml, exceeding normal values more than twice. The biological activity of IFNγ in these culture supernatants was significantly higher than those immediately after hormone therapy, whereas in 3–6-year-old group of patients it was also higher than baseline level. These results can serve as a laboratory justification for including recombinant IFNα-2b drugs in the therapy of such patients, presumably immediately after the end of hormone course. Overall, laboratory justified administration of interferon preparations seems to be necessary to determine optimal timepoint for applying such drugs to increase effectiveness for achieving a durable patient recovery.

IMMUNOLOGICAL CRITERIA FOR EFFECTIVE SYSTEMIC USE OF MURAMYL PEPTIDE IMMUNOMODULATOR IN THE TREATMENT OF PATIENTS WITH BURN INJURIES

Introduction. The problem of providing effective care to patients with burn injuries remains far from being finally solved. Due to significant immune disorders that occur against the background of thermal damage, the use of immunomodulatory drugs remains promising. Therefore, the aim of this study was to analyze the effectiveness of systemic use of the immunomodulatory drug Liastenum® in the complex treatment of patients with burn injuries. Materials and methods: The study involved 35 patients with burn injuries with the index of damage severity ranging from 30 to 60 units. Patients in the main group (n = 15) in addition to the usual treatment received an immunomodulator Liastenum®, which was administered intramuscularly at a dose of 2 mg once every 3 days (course dose — 10 mg). Treatment of patients in the comparison group (n = 20) did not involve the use of drugs with targeted immunocorrective action. Examination of patients included laboratory immunological examination of venous blood with assessment of various parts of the immune system and determination of the “Neutrophilic granulocytes form factor” indicator, which was performed on the 3rd, 14th, 21st day after the injury. The results of the study and their discussion. The obtained results allowed to confirm the ability of Liastenum® to stimulate the functional activity of neutrophilic granulocytes, restoring the phagocytic reserves of these cells, to normalize the level of lymphocytes and their individual subpopulation forms. In general, the action of the immunomodulatory drug was characterized by a balanced effect on the cellular, humoral parts of the immune system, phagocytosis. Conclusions. The effectiveness of systemic use of immunomodulatory drug Liastenum® in a comprehensive program of care for patients with burn injuries by balanced correction of immune disorders was laboratory established.

MAIN FACTORS OF DECOMPENSATION SYSTEM I NFLAMMATORY REACTION SYNDROME THE PATIENTS WITH ABDOMINAL SEPSIS

Summary. The goal of the robot is to determine the factors of decompensation of the systemic inflammatory response syndrome (SIRS) in abdominal sepsis (AS). Materials and methods. Based on the results of a comprehensive examination of 295 patients with AS according to the indicators of clinical and laboratory, biochemical, immunological examination and study of intra-abdominal pressure and the severity of enteral insufficiency, the leading factors in the development of DSIRS were determined. Results and discussion. It was found that against the background of secondary cellular immunodeficiency, the development of severe compartment syndrome with decompensated enteric insufficiency syndrome (EIS) was determined, which in combination deepened pathological changes with the progression of the inflammatory reaction and the development of organ failure. Indicators of the level of C-reactive protein 2.5 times, and procalcitonin 2.4 times were higher during hospitalization of patients with decompensated syndrome (P<0.001). With decompensation, a severe degree of SES was diagnosed 18.5 times more often, and with a compensated one, a mild degree of insufficiency was diagnosed 57 times more often, P <0.001. At the same time, a direct correlation was determined between the severe degree of EIS and symptoms of nausea (r = 0.420), vomiting (r = 0.573) and bloating (r = 0.251), (P <0.005). The immunoregulatory index (IRI) played the role of a marker of decompensation in patients with AS, (r = + 0.74, at p <0.01) with the development of secondary immunodeficiency, according to the T-suppressor type. In 60.8 % (n = 101) of cases with DSIRS, the fourth degree of intra-abdominal pressure was determined, on average it was (46.3 ± 6.3) mm, and I degree was determined only in the case of compensation, (P <0.001). More often in patients with DSIRS, the associations of gram-positive microorganisms and enterococci were determined — in 55.6 % and streptococci — in 38.1 % of cases. At the same time, in 81.3 % of cases, patients with DSIRS were diagnosed with aerobic-anaerobic mixed flora. Сonclusion. The obtained results of the study require the development of treatment methods that will effectively correct these pathogenetic changes in all directions in patients with AS.

Visceral Mycoses as a Cause of Severe HIV Infection and Death

<b><i>Introduction:</i></b> In recent years, there has been an increase in the number of systemic fungal infections among HIV-infected individuals. The article aimed to examine the frequency of invasive mycoses among the HIV-infected patients at the time of their urgent and/or planned admission to a specialized hospital. <b><i>Methods:</i></b> The diagnostic methods used in this study involved physical examination, laboratory testing, bacteriological examination, immunological examination, molecular genetic testing, and radiological imaging. The study was conducted under the ethical guidelines for retrospective studies and does not disclose data on individual patients. <b><i>Results:</i></b> Between 2016 and 2018, 85 HIV patients who died with HIV history underwent a series of clinical and pathomorphological examinations at the Novgorod Regional Infectious Diseases Hospital. Systemic mycoses frequently occur in the respiratory system and less often in the brain. Their incidence is severe and the mortality rates associated with it are high. In this study, PCP was the most common cause of death provoked by mycoses. <b><i>Discussion/Conclusion:</i></b> Systemic fungal disease can be diagnosed through a combination of diagnostic methods. A crucial factor in the reduction of mortality rates for systemic mycosis is the early diagnosis and intensive antimicrobial therapy.

CHARACTERISTICS OF SOME IMMUNOLOGICAL INDICATORS OF HIV INFECTION IN COMBINATION WITH TUBERCULOSIS

The purpose of the work is to carry out a comparative analysis of epidemiological, clinical and individual laboratory parameters of groups of patients with HIV infection associated with tuberculosis (TB) and TB monoinfection. Patients and methods. A comprehensive immunological examination was performed on 231 patients, including 155 HIV-infected with active newly diagnosed tuberculosis and 76 on tuberculosis alone. The HIV/TB group was divided into 3 subgroups depending on the time of TB accession to HIV infection. The levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) were compared for groups with co-infection with HIV/TB and patients with TB monoinfection. Results. In associated HIV/TB infection, the level of CD4+T-lymphocytes is significantly lower compared to patients with TB monoinfection. In the HIV/TB group, it was established the presence of a medium feedback force between the number of CD4+T-lymphocytes and the serum concentration of IFN-γ (correlation coefficient r=-0.36, confidence level P<0.05); weak direct relationship between viral load and serum IFN-γ concentration (r=0.25, P<0.05); medium strength inverse relationship between the number of CD4+T-lymphocytes and the level of viral load (r=-0.44, P<0,01). In the group with TB monoinfection, no correlation was found between the number of CD4+T-lymphocytes and cytokine parameters. Conclusions. In associated HIV/TB infection, CD4+T-lymphocyte counts are significantly lower than in patients with TB only. As HIV infection progresses (decrease in CD4+T-lymphocytes and increase in HIV load), there is an increase in serum IFN-γ and IL-4, which probably indicates a decrease in the number of anti-inflammatory T-regulatory cells, or a decrease in their suppressor activity.