Vol 21, No 1 (2024)

The review presents the current understanding of the mechanisms of initiation and development of hypersensitivity reactions triggered by external factors, based on the new 2023 nomenclature of allergic diseases proposed by the European Academy of Allergy and Clinical Immunology. It details the new concept of hypersensitivity, which systematizes previous classifications and summarizes the new data on the etiology and mechanisms of inflammatory reactions in comparison with diverse immune response variants, based on the concept of disease phenotypes and endotypes. The today’s concept of allergic reactions covers several types: those associated with antibody formation (I–III), cell-mediated reactions (IVa–c) and the Pichler concept, tissue-dependent ones caused by the epithelial barrier defects and metabolism-induced immune dysregulation (V–VI), and direct immunoinflammatory reactions to chemicals (VII). In the updated classification, both adaptive and innate immune responses actively participate in initiation and effector phases of the hypersensitivity reactions. The review highlights the role of regulatory and effector lymphocyte subpopulations and innate lymphoid cells in various types of hypersensitivity. It also reports a pivotal role of epithelial barrier dysfunction in many allergic diseases and the effect of viral infections on their courses. The significance of the metabolic dysregulation and its impact on the immune response is emphasized. According to the nomenclature of allergic reactions, several pathophysiological mechanisms may underlie the development of a same disease. Notably, various hypersensitivity mechanisms involve most cellular and humoral factors, reaffirming the universal biological nature of immune response. As awareness of the new concept grows and clinical and experimental data accumulate, the updated classification of the hypersensitivity types will contribute to a theoretically substantiated and practically effective framework for the prevention, accurate diagnosing, and improved treatment of allergic diseases.

Epstein–Barr virus is the most widespread herpes virus in humans; the majority of the global population is infected by it. In children, the viral infection either lacks symptoms or leads to infectious mononucleosis. In a small percentage of people with latent infection, especially immunosuppressed patients, Epstein–Barr virus causes lymphoid and epithelial malignant neoplasms and a number of autoimmune diseases. Among other things, it is one of the causes of multiple sclerosis. Innate immunity is the primary protection from viruses, which the virus evades by using a number of strategies for successfully infecting people. It disrupts the innate immunity’s signaling pathways activated by Toll-, NOD-, RIG-I- and AIM2-like receptors, as well as cyclic GMP-AMP synthase. Epstein–Barr virus also counters the production and signaling of interferon, including JAK-STAT and TBK1-IRF3 pathways. Because of the differential modulation of the proviral and antiviral mechanisms of caspases and other cell cycle regulators at different infection stages, the virus actively interferes with the apoptosis and inflammation pathways to proceed infecting effectively. Using the activation of innate immunity to its advantage by triggering the pro-inflammatory response and the proteolytic cleavage of caspases which demonstrate proviral activity, the virus establishes latency and enters the phase of lytic reactivation. This promotes the development of serious life-threatening conditions, including cancer. The outcome of the infection is regulated by the delicate interaction between innate and adaptive immunity and the virus’ reproduction. In the absence of approved prophylactic vaccines, immunocorrection and antiviral therapy are the only possible methods of combating the virus and preventing the conditions associated with it. Understanding the mechanisms of various genes of Epstein–Barr virus involved in its life activity at different infection stages will help to find the right approach to developing preventive and curative treatments for this virus in the future.

Vitamin D plays a major role in bone metabolism regulating body phosphorus and calcium metabolism. Vitamin D binding protein (VDBP) binds to vitamin D metabolites and transports them to target tissues. It is hypothesized that polymorphisms in VDBP affect the absorption of vitamin D in the body. However, the relationship between VDBP polymorphisms and vitamin D levels in individuals with obesity has yet to be sufficiently investigated.

This work aimed to identify the relationship between vitamin D [25(OH)D₃] blood levels in obese and non-obese individuals and the rs4588 and rs7041 polymorphisms in VDBP.

The study included a total of 80 participants from the Kaliningrad region. The sample was stratified based on vitamin D status (normal, insufficiency, deficiency, and acute deficiency) and body mass index (BMI). Vitamin D blood levels were determined using enzyme immunoassay. Genomic DNA was extracted from whole blood samples. VDBP polymorphisms were identified using HaeIII and ErhI restriction endonucleases.

No significant differences in vitamin D blood levels between obese and non-obese individuals were revealed. The rs4588 C > A genotypes were associated with no significant differences in vitamin D levels between individuals with different body mass index (CC, p=0.147; CA, p=0.646; AA, insufficient data). However, for the VDBP rs4588 polymorphism, a significant difference was demonstrated in allele frequency between the groups with different vitamin D levels, i.e., normal vitamin D level group vs. insufficiency group (p=0.009) and normal vitamin D level group vs. acute deficiency group (p <0.0001).

The analysis of the individuals with the VDBP rs7041 T > G polymorphism demonstrated that there were no significant differences in the vitamin D levels between the BMI groups with specific genotypes (TG, p=0.502; GG, p=0.283; TT, insufficient data). However, the control and acute deficiency groups differed significantly (p <0.0001) in allele frequencies of individuals with the rs7041 polymorphism.

Vitamin D blood levels in obese patients were comparable to those of non-obese individuals. VDBP rs7041 and rs4588 polymorphisms do not correlate with variations in vitamin D blood levels among individuals with different BMI. However, the VDBP rs4588 A polymorphism is associated with low vitamin D levels, while the VDBP rs4588 G polymorphism is more common among individuals with normal vitamin D blood levels.

The immune system is one of the main regulatory homeostatic systems in the human body. The immune homeostasis is maintained by numerous versatile mechanisms. Immune system dysfunction leads to various immunopathological conditions. One of the major challenges is identifying immune system diseases and clinical conditions associated with reversible immune system dysfunctions. In the first case, these conditions may be determined as persistent immune dysfunctions; in the second case, as transient ones. Immunopathological conditions are manifested by various immunological symptoms and signs (syndromes) disrupting normal bodily functions as a result of immune system impairment. Accordingly, clinical practice implies the need to detect a particular immunopathological syndrome, determine its characteristics, assess its severity, identify its causes, perform additional laboratory studies and clinical investigations, and establish a specifically immunological diagnosis. However, no general clinical criteria for diagnosing immunopathological conditions are presently available. A discussion is proposed to be held in order to identify and describe the clinical symptoms associated with dysfunctions of various immune system components. This will serve as a valuable reference for practicing physicians who conduct immunoactive therapy.