Vol 23, No 1 (2026)

Advances in Immunology have led to the understanding that the immune system is not only involved in the pathogenesis of various diseases but also plays a key role in maintaining homeostasis and tissue repair. It mediates interactions between the organism and dietary as well as environmental antigens, supports pregnancy, and enables coexistence with the microbiota, highlighting its role as an integrative system of the body.

This review examines the term immunome in both narrow and broad senses, describes key achievements of the Human Immunome Project, and discusses the advantages of this approach for studying the immune system. Initially, the term immunome referred to the repertoire of rearranged antibody genes, as well as T- and B-cell antigen receptors (TCR and BCR). The AIRR-seq technology has been developed for the collection and analysis of adaptive immune receptor repertoires. Knowledge of TCR and BCR repertoires can be applied to the development of modern vaccines against highly dangerous pathogens, rapid vaccine design in response to emerging pathogens, and the creation of personalized vaccines for elderly individuals and specific patient groups. An example of successful application of immunome research in the narrow sense is the development of a Russian drug for the treatment of ankylosing spondylitis. With substantial advances in immunology and biotechnology, the concept of the immunome has expanded. In its broader definition, the immunome includes not only immunocompetent cells, their receptors, and the molecules they produce, but also nonimmune cells and molecules involved in regulating immune responses, as well as the microenvironment in which immune reactions occur. Studies identifying changes in immune cell phenotypes, receptors, transcripts, cytokines, and their associations with disease activity or subtype provide valuable insights. However, their fragmented nature complicates the identification of the pathogenic role of individual factors.

Comprehensive analysis of the immunome facilitates the understanding of immunopathogenesis, the discovery of biomarkers for various diseases, patient stratification, and personalized therapy selection. The extreme complexity of the immunome and its internal interactions necessitates the use of advanced mathematical modeling, bioinformatics, computational tools, and rapidly developing artificial intelligence technologies.

BACKGROUND: Elevated serum creatinine levels and proteinuria are currently considered indicators of kidney damage; however, these markers typically appear at late stages, when renal injury is often irreversible and the effectiveness of pharmacotherapy is limited. Therefore, the identification of biomarkers for early diagnosis of kidney damage may remarkably improve the effectiveness of nephroprotective therapy.

AIM: This work aimed to evaluate the association between levels of proinflammatory cytokines (IL-6 and IL-1β) and renal functional parameters in patients with varying degrees of obesity.

METHODS: A prospective analysis of diagnostic data from 52 patients of both sexes was performed. Participants were divided into two groups based on glomerular filtration rate. Inclusion criteria were age 35–65 years and the presence of obesity; exclusion criteria included confirmed diabetes mellitus, hypertension, and other acute inflammatory conditions.

RESULTS: Both IL-6 and IL-1β demonstrated acceptable diagnostic accuracy (AUC >0.74) in identifying patients with early decline in glomerular filtration rate. These findings suggest that these cytokines may serve as potential biomarkers of early-stage chronic kidney disease associated with obesity, including in patients without comorbid chronic conditions.

CONCLUSION: The cytokine profile can serve as a biomarker for the early diagnosis of metabolic dysfunction–associated kidney damage. This facilitates the development of targeted anti-inflammatory therapy strategies for the prevention of chronic kidney disease in patients with obesity.

BACKGROUND: Objective criteria for assessing the severity of recurrent genital herpes remain insufficiently developed. Standard clinical approaches do not always reflect the extent of underlying immunological disturbances. The role of innate immunity parameters, particularly natural killer (NK) cells and interferons (IFN-β, IFN-γ, IFN-λ3, and IFN-λ1), as biomarkers of disease severity has been investigated only incompletely, limiting the timely selection of appropriate treatment strategies.

AIM: To perform a comparative analysis of selected innate immunity parameters in patients with recurrent genital herpes in order to identify the most informative biomarkers determining disease severity.

METHODS: A cross-sectional, single-center observational study was conducted and included 56 patients with a confirmed diagnosis of recurrent genital herpes treated at the Yutskovskikh Professorial Clinic (Vladivostok, Russia). Study groups were formed according to the annual recurrence rate (mild, moderate, and severe disease). Laboratory assessment included the evaluation of cellular and cytokine components of innate immunity: serum concentrations of IFN-β, IFN-γ, IFN-λ3, and IFN-λ1 were measured using enzyme-linked immunosorbent assay (ELISA), while NK cell levels were determined by flow cytometry. Statistical analysis was performed using the Shapiro–Wilk test; group comparisons were conducted using the Kruskal–Wallis test. Correlations were assessed using Spearman’s rank correlation coefficient, and the strength of associations was interpreted according to Chaddock’s scale.

RESULTS: Analysis of data from 56 patients distributed across the study groups demonstrated that NK cell levels and IFN-β concentrations were the principal biomarkers of disease severity (p < 0.001 and p = 0.001, respectively). A progressive decline in median values was observed, reaching a twofold reduction for NK cells and more than a fourfold reduction for IFN-β. IFN-γ levels were significantly lower in patients with severe disease compared with those with mild disease (p_III–I = 0.020), with the median value decreasing by nearly half. No statistically significant differences were identified for IFN-λ3 or IFN-λ1 (p = 0.376 and p = 0.412, respectively); however, complete absence of serum IFN-λ3 was detected in 39.3% of patients. A statistically significant weak positive correlation was found between NK cell levels and IFN-β concentrations (ρ = 0.265; p = 0.049). Correlations between NK cells and IFN-γ or IFN-λ3 were not statistically significant, while no association was observed with IFN-λ1.

CONCLUSION: NK cell levels and IFN-β concentrations were identified as the primary biomarkers whose stepwise decline significantly reflects increasing disease severity. The observed correlation between these parameters and the absence of IFN-λ3 production in 39.3% of patients support the combined suppression of cellular innate and mucosal immunity with increasing severity of recurrent genital herpes. These findings underscore the need for further investigation in a larger-scale study.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel in humans and other vertebrates, whose mutation leads to cystic fibrosis. CFTR inhibitory factor, or Cif, is a recently discovered bacterial epoxide hydrolase that downregulates CFTR protein upon the bacterial infection. However, its cleaving activity has been recently characterized towards fatty acid epoxides—epoxygenase-derived oxylipins. We identified a list of host-associated bacteria with putative Cif proteins, identified their most prevalent ecological functions within a systematic review, and performed similar review for the previously assembled list of host-associated bacteria carrying lipoxygenase (LOX). Both Cif and LOX showed the association with pathogenesis and symbiosis in broad host range, and similar ecological profiles of their carriers suggested that they both might target oxylipin signaling in hosts. We also described the association of Cif with plant hormone biosynthesis and plant growth promotion, which indirectly supports our previous model of bacterial LOX action in plant and vertebrate hosts.