卷 21, 编号 4 (2024)

This article continues our series of works devoted to the diagnosis of immunopathological syndromes in various diseases. The analysis of these syndromes provides deeper insight into the pathogenetic mechanisms underlying disease development, which is critically important for timely diagnosis and effective therapy. The present study examines immunopathological syndromes associated with adaptive immunity. Systemic immunopathological reactions of the cellular and humoral components of the immune system are characterized, and syndromes typical of type I, II, and III cellular responses are identified. Manifestations associated with impaired immunosuppression are also described. In evaluating immunopathological syndromes of the humoral immune system, differentiation by immunoglobulin classes—A, M, E, and the four subclasses of immunoglobulin G—is proposed. In this discussion article, we aim to unify the definitions of immunopathological syndromes related to adaptive immunity. Our primary goal is to provide clinicians with conceptual foundations for understanding their mechanisms of formation, thereby opening new therapeutic opportunities. We also seek to standardize key approaches to the assessment, staging, and treatment of these syndromes.

Background: Coronavirus disease 2019 (COVID-19) is a multisystem disease caused by severe immune response dysregulation, which leads to the overproduction of proinflammatory cytokines and a cytokine storm. The most significant mediators of systemic inflammation are IL-6, IL-8, and IL-10, as well as IFN-α and IFN-γ. Levels of these mediators reflect the degree of activation of the inflammatory cascade and the severity of damage to target organs. Detecting cytokine abnormalities at admission can predict and facilitate early risk stratification for adverse outcomes, which is especially important during periods of high strain on the healthcare system.

Aim: This study aimed to evaluate the levels of key proinflammatory cytokines in 617 patients with confirmed COVID-19 to assess the severity of the acute inflammatory response and its correlation with disease severity and clinical outcomes.

Methods: This was a non-randomized clinical study of 617 hospital cases, including 255 men and 362 women aged 59–78 years, who were admitted to the Infectious Diseases Hospital of the Bashkir State Medical University Clinic from 2020 to 2021. Patients were grouped by disease severity: moderate (n = 502), severe (n = 67), and fatal (n = 18). On day 1 of hospitalization, levels of IL-1, IL-6, IL-8, IL-10, IFN-α, and IFN-γ were measured in serum samples using an enzyme-linked immunosorbent assay (Vector-Best JSC). Statistical analysis was performed using Statistica 10 and StatTech 4.0.7 with ROC modeling to determine predictive cutoffs.

Results: Most of those who died were over 68 years old, and the risk of death increased significantly for those over 74 years old. A higher mortality rate was observed in patients who were hospitalized for less than 13 inpatient days (p = 0.042). Significantly higher levels of IL-6 and IL-10 were reported in severe and fatal cases (p < 0.001). The level of IFN-γ was significantly lower in fatal cases (p < 0.024). The decrease in IFN-α and IFN-γ levels indicated an inadequate interferon response. A ROC analysis identified the following predictive threshold cutoffs for a fatal outcome: IFN-α ≥ 7.292, IL-10 ≥ 8.796, and IL-6 ≥ 23.061.

Conclusion: The COVID-19 severity and mortality were associated with higher levels of proinflammatory interleukins (IL-6 and IL-10) and lower levels of interferons (IFN-α and IFN-γ). These parameters can be considered predictive biomarkers, which could improve management strategies and enable early risk stratification.

Background: Influenza and other acute respiratory viral infections are among the leading causes of infectious morbidity in children. Early determination of influenza severity and identification of the risk of complications represent an important focus for studying and identifying the most informative prognostic markers.

Aim: This study aimed to develop a severity prediction model for seasonal influenza in children based on clinical-laboratory data, cytokine profile parameters, and indices of the lipid peroxidation–antioxidant defense system during the early stages of the disease.

Methods: A cohort study included 104 children with polymerase chain reaction-confirmed influenza. The study was carried out at the Irkutsk Regional Infectious Clinical Hospital during the 2018–2019 seasonal epidemic rise. Plasma levels of spontaneous cytokine production (IL-1β, IL-4, IL-6, IL-8, TNF-α, IFN-α, IFN-γ) and high-sensitivity C-reactive protein (hsCRP) were measured by enzyme-linked immunosorbent assay; indices of the lipid peroxidation–antioxidant defense system were assessed by spectrophotometric and fluorometric methods.

Results: Influenza in children manifested with catarrhal symptoms and intoxication syndrome. Significant increases were observed for IL-1β (×940), IL-4 (×260), IL-8 (×63.44), TNF-α (×4.34), IFN-γ (×3.97), IL-6 (×43.77), IFN-α (×2090), and hsCRP (×31.76). Across all age groups, levels of retinol (×1.41 decrease), α-tocopherol (×1.46 decrease), total antioxidant activity (×1.02 decrease), GSH and GSSG (×1.16 decrease) were significantly reduced. Logistic regression identified the most informative severity predictors among 94 clinical-laboratory variables: maximum body temperature at admission (p = 5.0×10⁻⁴), presence of pneumonia (p = 3.0×10⁻⁴), hsCRP (p = 3.1×10⁻⁴) and ketodienes–conjugated trienes (p = 3.1×10⁻⁴).

Conclusions: Seasonal influenza in children is characterized by marked elevation of pro- and anti-inflammatory cytokines across age groups combined with deficiency of key antioxidant defense factors. Measurement of maximum body temperature at admission, identification of pneumonia, and determination of hsCRP and ketodienes–conjugated trienes levels enables severity prediction. The proposed prediction algorithm is practical and may be recommended for clinical use.

August 26, 2024, marked the 85th birthday of Tatyana Mikhailovna Andronova, a prominent chemist, Cand. Sci. (Chemistry), the founder and head of the pharmaceutical company Pepteck. Her career is inseparable from the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, where she has worked for over 50 years, rising from laboratory assistant to lead developer.

Andronova is a worthy successor to her family: her father, M.A. Andronov, was a renowned chemist who developed a method for extracting the amino acid L-arginine. Her key achievement was the method to synthesize glucosaminylmuramyl dipeptide, which she developed in 1976. This enabled industrial-scale production of the highly effective immunomodulator Likopid®, which has been successfully used in clinical practice for almost three decades. Andronova was awarded the Russian Federation Government Award for her contribution to the organization of biotechnological production.

This article highlights Andronova’s numerous scientific and industrial achievements, emphasizing the unbroken scientific dynasty, current scientific developments supervised by her, and her contribution to Russian pharmaceutics.