Vol 26, No 1 (2023)

Partial or complete loss of teeth occurs in elderly and senile people, caused, mainly, by chronic generalized periodontitis. At the same time, the impact of presence or absence of persisting teeth and periodontium, is practically not covered in the literature as a factor of balance in the oral cavity, including local immunity of the mucous membranes. Our work concerned the changes in local immunity of the oral cavity occuring with the loss of natural teeth. We have observed 45 elderly people who were divided into 3 study groups, i.e., without inflammatory periodontal pathology (1), with periodontitis (2) and with chronic periapical inflammatory processes in the absence of periodontal inflammation (3). In order to sanitize oral cavity before the upcoming dental prosthetics, the patients of study groups 2 and 3 underwent extraction of all teeth in the upper and lower jaws. Indices of local immunity of the oral cavity in the salivary fluid of patients were assessed before surgical sanitation of the oral cavity (before the teeth extraction) and 30-35 days after removal of the last tooth. We have measured the salivary levels of secretory immunoglobulin A (sIgA) as well as pro-inflammatory cytokines, i.e., interleukin-1â (IL-1â), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-á (TNFá), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10)), as well as contents of antimicrobial peptides in saliva (catelicidin LL-37 and alphadefensins 1-3 (HNP1-3). We have found that the development of inflammation in severe inflammatory periodontal diseases, in particular, chronic generalized periodontitis requiring tooth extraction for oral cavity sanitation is characterized by functional insufficiency of secretory immunity of the oral mucosa associated with decreased secretion of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin, as well as a shift in the salivary cytokine balance towards increased production of pro-inflammatory cytokines. Removal of teeth, as the main source of inflammation and the basis for maintenance of dysbiotic microbiome biofilm leads to elimination of inflammation and the restoration of immune balance in the oral cavity.

Immunological research of steroid-depended chemical carcinogenesis in humans is based on positive experience in the clinical usage of selective estrogen receptor modulators and experimental design of immunological methods for human protection from environmental carcinogens. Our study aimed for research of idiotypic antibodies against benzo[a]pyrene, estradiol and progesterone (IgA₁-Bp, IgA₁-E2 and IgA₁-Pg), in connection with anti-idiotypic antibodies specific to estradiol and progesterone (IgG₂-E2 and IgG₂-Pg) in serum samples of postmenopausal healthy women (HW) and ER⁺/PR⁺ stage I breast cancer patients (BCP). Idiotypic antibodies were studied in 402 HW and 475 BCP using ELISA technique, with BP, E2 and Pg conjugated with bovine serum albumin as adsorbed antigens. The anti-idiotypic antibodies were studied using ELISA method and monoclonal antibodies against E2 and Pg as adsorbed antigens. High individual ratios of IgA₁-Bp/ IgA₁-Pg > 1 and IgA₁-E2/IgA₁-Pg > 1 were revealed in 42.1% and 48.5% HW, and in 71.1% and 78.1% of BCP cases (p < 0.0001, OR = 5.9 and OR = 3.8, respectively). High IgG₂-E2 > 4 levels were found in 23.4% HW and in 41.2% of BCP group (p = 0.0001, OR = 2.3). Combination of IgA₁-Bp/IgA₁-Pg ≤ 1 with IgG₂-E2 ≤ 4 and IgG₂-Pg > 2 was more common in HW, than in BCP (29.3% vs 5.8%, p < 0.0001, OR = 0.1). Combinations of IgA₁-Bp/IgA₁-Pg > 1with IgG₂-E2 > 4 or with IgG₂-Pg > 2 were more frequent in BCP, than in HW (12.0% and 31.8% vs 4.9% and 15.2%, accordingly, p = 0.01, OR = 2.7 and p = 0.001, OR = 2.6), as well as combination of IgA₁-Bp/IgA₁-Pg > 1 with IgG₂-E2 > 4 and IgG₂-Pg > 2 (23.4% vs 9.8%, p = 0.0003, OR = 2.8). Similar specific features were found in HW and BCP when studying IgA₁-E2/IgA₁-Pg ratio with IgG₂-E2 and IgG₂-Pg. Nevertheless, high IgA₁-Bp/IgA₁-Pg > 1 or IgA₁-E2/IgA₁-Pg > 1 combined with low IgG₂-E2 ≤ 4 + IgG₂-Pg ≤ 2 were revealed in HW (27.7% and 28.8%) more frequently, than in BCP (19.7%, p = 0.06 and 17.9%, p = 0.008). Excess of IgA₁-Bp and IgA₁-E2 levels over IgA₁-Pg in combination with high IgG₂-E2 and IgG₂-Pg levels in HW is associated with ER⁺/PR⁺ BC stage I condition and may serve as an marker for preventive BC therapy by the targeted ER modulators.

Significant changes in cellular and humoral immunity are observed in new coronavirus infection (COVID-19). The “cytokine storm” develops in cases of severe clinical course, being accompanied by significantly increased levels of pro-inflammatory cytokines, often associated with suppression of immune response. At the same time, the prediction of the immune status is an urgent task, thus allowing timely correction of current therapy. The aim of our research was to evaluate predictive capability for the immune system changes on the 6^th day of COVID-19 disease when using standard therapy, or with addition of immunocorrector thymalin to the treatment regimen. A retrospective study was conducted in 87 patients with severe COVID-19. All patients were divided into 2 groups, i.e., (1) controls who received basic treatment; (2) basic treatment supplied with thymalin (10 mg, intramuscular injections daily for 5 days). Assessment of severity and clinical course of COVID-19, and basic treatment regimen for the patients corresponded to current version of the interim Guidelines from the Ministry of Health of the Russian Federation “Prevention, diagnosis and treatment of a new coronavirus infection COVID-19”. Laboratory studies included complete blood counts, immunogram parameters with the calculation of the ratio of certain types of leukocytes were performed on the 1st and 6th days of observation. Statistical evaluation was made using scripts of the specialized statistical analysis language R (http://cran.r-project.org) version 4.1.3. The blood parameters were evaluated using the binary classification method. The changes in parameters of cellular immunity were classified by means of ROC-analysis.

We have found that the basic therapy of severely ill COVID-19 patients was not followed by recovery of immune status on the 6th day from the start of treatment. At marginal level, one can only suggest a probable prediction of increase in WBC and MON counts, a decrease in CD4⁺, NK and CD8⁺perNK, as well as the CD4⁺/CD8⁺ ratio. Addition of thymalin to the basic therapy is largely accompanied by the normalization of immunogram parameters. At the same time, it is possible to predict, with “excellent” rating, an increased number of T-LIM, including CD4⁺ and B-LIM, and, with “good” rating, an increase in the total numbers of LIM, as well as CD8⁺, HLA-CD3⁺DR⁺ and NK cells. The data obtained in severe cases of COVID-19 make it possible to predict changes in immune status, and, hence, the course of the disease, at a high degree of probability.

Bacteria are known both to exhibit anticytokine activity (ACA), i.e., to secrete extracellular compounds which inactivate / neutralize various cytokines, and to produce cytokine-like substances (CPV) released to the culture medium. At the same time, the ability of Candida to secrete such substances has not been previously studied. The purpose of our study was to determine the presence of ACA and the ability to produce CPV in Candida strains isolated from the reproductive tract of apparently healthy pregnant women.

The experimental series included 26 clinical strains of Candida spp. isolated from vaginal secretions. Isolation and identification of fungal species was based on morphological and biochemical criteria. ACA against IL-4, IL-6, IL-8, IL-10, IL-17A and TNFá were detected following 2-hour co-incubation of fungal suspensions with solutions of the distinct cytokines at a ratio of 1:1. Determination of the cytokine concentrations was carried out by ELISA using the “Cytokin” kits (St. Petersburg). ACA amounts were defined as the percentage of cytokine inactivation in experimental samples compared to the control expressed as pg/mL. Their ability to produce CPV was expressed as percentage of cytokine production in experimental specimens compared to the controls (pg/mL). The obtained data were subjected to statistical evaluation.

ACA of Candida spp. and their ability to produce CPV were revealed for the first time. with appropriate differences established between the studied Candida species, i.e., cultures of C. non-albicans showed ACA more often for the pro-inflammatory cytokines; C. albicans isolates showed more frequent production of the substances, similar to the pro-inflammatory cytokines IL-8, IL-17A, and TNFá. Expression of ACA against IL-10 and ability to produce the anti-inflammatory IL-4- and IL-10-like substances were significantly higher in the cultures of C. non-albicans species.

The results of these experiments expand our knowledge on the spectrum of Candida biological activities and require further study.

There is a steady increase in the prevalence of allergic diseases of atopic origin worldwide, e.g., atopic bronchial asthma (ABA) and atopic dermatitis (AD). Identification of a causally significant allergen in allergic patients is crucial for the diagnosis, therapy and prevention of allergic diseases. Korea has developed the Allergy-Q^® multiplex test to detect specific IgE. Allergy-Q^® is based on an immunoblotting method using a nitrocellulose membrane as a solid phase for allergen immobilization and can detect allergen-specific IgE simultaneously to 107 allergens. Our aim was to conduct a comparative analysis for detectable allergen-specific IgE antibodies to food, fungal, pollen, household, epidermal allergens in blood serum by immunoblotting method using the Allergy-Q^® test system in patients with atopic dermatitis, atopic bronchial asthma and psoriasis.

The study included patients with atopic dermatitis (AD, group 1, n = 9), atopic bronchial asthma (ABA, group 2, n = 14) and psoriasis (PS, group 3, n = 17). The concentration of total immunoglobulin E and allergen-specific immunoglobulins of class E in blood serum to 32 most common food, fungal, pollen, household, epidermal allergens was determined by the immunoblotting method using the Allergy-Q^® test system (Korea).

We have found that sensitization of atopic origin was observed in all patients with AD (n = 9), in 85.7% (n = 12) of patients with atopic bronchial asthma, and in 47.1% (n = 8) of patients with psoriasis. Polyvalent sensitization was shown to prevail in all groups of the examined persons. When studying the spectrum of sensitization to food allergens, a significantly increased frequency of positive reactions to cow’s milk protein was found in the group of patients with AAA as compared with AD and PS groups. Among all studied groups, sensitization to the Alternaria fungi was found at the highest frequency in the group of patients with ABA. Sensitization to ragweed pollen was very common in all groups of patients. Sensitization to household and epidermal allergens in the groups with AD and AAA was noted for all studied allergens with the highest positivity rates for the feline epithelium and dog dander.

In the present study, the Allergy-Q^® system showed an agreement with preliminary data from a specific allergological examinations. This relationship suggests a potential for usage of the Allergy-Q^® immunoblotting method as a highly effective alternative to other in vitro tests for diagnosing atopy. An advantage of the Allergy-Q^® Multiplex Serum Allergen-Specific IgE Detection Kit is a short processing time, small amount of blood sample, and broader clinical information on the causative allergens.

Identification of primary immunodeficiencies (PID), distinction of their nosological forms and timely admoinistered therapy for this disorders frepresent topical problems of modern immunology. According to the PID registry of the National Association of Experts in the Field of Primary Immunodeficiencies (NAEPID), as of 2021, 3617 cases of this disease were diagnosed in Russian Federation (RF). The prevalence of PID in Russian Federation is 2.48 per 100,000 population. Currently, autoinflammatory syndromes (AIS) comprise rare, genetically determined disorders. According to the NAEPID registry data, of the PID register, 541 cases of autoinflammatory syndrome (AIS) were registered in the Russian Federation (2021). Timely diagnosis of AIS is especially important in young children who have similar phenotypic signs, in order to reduce the number of deaths and prevent disability. According to the PID registry, the median diagnostic delay in Russia is 27 months. The purpose of this work is to update information about the autoinflammatory syndrome that clinicians may encounter, e.g., pediatricians, rheumatologists, hematologists and other specialists. This syndrome requires a complex differential diagnostic algorithm for clinicians and is often subject to multidisciplinary approach, involving specialists of different profile. This article describes a clinical case of a 3-year-old child S. with a diagnosis of Primary immunodeficiency: autoinflammatory syndrome, undifferentiated. The patient was diagnosed since the age of 5 months, when periodic rises in body temperature to febrile values were registered once a month. Later on, the fever episodes were observed 2 times a month. The diagnosis was made at the place of residence as secondary immunodeficiency virus-associated state (CMV infection). CMV viremia was canceled against the background of ongoing treatment, but the inflammatory attacks persisted. Molecular genetic studies did not reveal any defects. In view of poor response to NSAID therapy and prednisone prescribed at a dose of 1-1.5 mg/kg/day, he was admitted to the Dmitry Rogachev Research Medical Cemter. The child was finally diagnosed with PID, and therapy was initiated with a selective competitive inhibitor of TNFa – etanercept at a dose of 0.8 mg/kg/day once a week. Hence, the autoinflammatory syndrome in children is difficult to diagnose and select therapy, and it may be unfavorable prognostically.