Antibody-dependent enhancement (ADE) is a phenomenon where virus-specific antibodies paradoxically cause enhanced viral replication and/or excessive immune responses, leading to infection exacerbation, tissue damage, and multiple organ failure. ADE has been observed in many viral infections and is supposed to complicate the course of COVID-19. However, the evidence is insufficient. Since no specific laboratory markers have been described, the prediction and confirmation of ADE are very challenging. The only possible predictor is the presence of already existing (after previous infection) antibodies that can bind to viral epitopes and promote the disease enhancement. At the same time, the virus-specific antibodies are also a part of immune response against a pathogen. These opposite effects of antibodies make ADE research controversial. The assignment of immunoglobulins to ADE-associated or virus neutralizing is based on their affinity, avidity, and content in blood. However, these criteria are not clearly defined. Another debatable issue (rather terminological, but no less important) is that in most publications about ADE, all immunoglobulins produced by the immune system against pathogens are qualified as pre-existing antibodies, thus ignoring the conventional use of this term for natural antibodies produced without any stimulation by pathogens. Anti-glycan antibodies (AGA) make up a significant part of the natural immunoglobulins pool, and there is some evidence of their antiviral effect, particularly in COVID-19. AGA have been shown to be involved in ADE in bacterial infections, but their role in the development of ADE in viral infections has not been studied. This review focuses on pros and cons for AGA as an ADE trigger. We also present the results of our pilot studies, suggesting that AGAs, which bind to complex epitopes (glycan plus something else in tight proximity), may be involved in the development of the ADE phenomenon.

Population screening of newborns is an extremely important and informative diagnostic approach that allows early identification of babies who are predisposed to the development of a number of serious diseases. Some of these diseases are known and have effective treatment methods. Neonatal screening enables the early diagnosis and subsequent timely initiation of therapy. This helps to prevent serious complications and reduce the percentage of disability and deaths among newborns and young children. Primary immunodeficiency diseases and primary immunodeficiency syndrome (PIDS) are a heterogeneous group of diseases and conditions based on impaired immune system function associated with developmental defects and characterized by various combinations of recurrent infections, development of autoimmune and lymphoproliferative syndromes (genetic defects in apoptosis, gene mutation Fas receptor or ligand), granulomatous process, and malignant neoplasms. Most of these diseases manifest in infancy and lead to serious illness, disability, and high mortality rates. Until recently, it was impossible to identify children with PIDS before the onset of the first clinical symptoms, which are usually accompanied by complications in the form of severe coinfections of a viral-bacterial-fungal etiology. Modern advances in medical laboratory technology have allowed the identification of children with severe PIDS, manifested by T- and/or B-cell lymphopenia and other disorders of the immune system. This review discusses the main existing strategies and directions used in PIDS screening programs for newborns, including approaches to screening based on excision of T-cell receptors and kappa-recombination excision circles, as well as the potential role and place of next-generation sequencing technology to increase the diagnostic accuracy of these diseases.

Arterial hypertension (AH) is a leading risk factor for the development of cardiovascular, cerebrovascular, and renal diseases, which are among the top 10 most common causes of death in the world. The etiology of hypertension has not been fully elucidated, but it has been established that endothelial dysfunction is the most significant pathogenetic link in the formation and progression of the disease. The data obtained in the last 10-15 years on endothelial glycocalyx (eGC) studies indicate that endothelial dysfunction is preceded by destabilization and shedding of eGC with the appearance of its soluble components in the blood, which is equivalent to a process that can be designated as eGC dysfunction. Signs of eGC dysfunction are expressed in the development of hypertension, diseases of the cardiovascular system, and their complications. The purpose of this review is to analyze and substantiate the pathophysiological role of eGC dysfunction in hypertension and cardiovascular diseases and to describe approaches for its assessment and pharmacological correction. Abstracts and full-size articles of 425 publications in Pubmed/MEDLINE databases over 20 years were studied. The review discusses the role of eGC in the regulation of vascular tone, endothelial barrier function, and anti-adhesive properties of eGC. Modifications of eGC under the influence of pro-inflammatory stimuli, changes in eGC with age, and with increased salt load are considered. The aspect associated with eGC dysfunction in atherosclerosis, hyperglycemia and hypertension is covered. Assessment of eGC dysfunction is difficult but can be performed by indirect methods, in particular by detecting eGC components in blood. A brief description of the main approaches to pharmacoprevention and pharmacocorrection of hypertension is given from the position of exposure effects on eGC, which currently has more a fundamental than practical orientation. This opens up great opportunities for clinical studies of eGC dysfunction for the prevention and treatment of hypertension and justifies a new direction in the clinical pharmacology of antihypertensive drugs.

Objective: In a prospective cohort study to evaluate the clinical and immunological efficacy of differentiated targeted interferon and immunomodulatory therapies focused on identified pathological immunophenotropes and associated clinical manifestations in immunocompromised patients suffering from atypical chronic active herpes viral infections (ACA-HVI).Materials and methods: 335 patients suffering from mixed-AHA-HVI were examined. The study complex included: methods for detecting herpesviruses: serodiagnosis, PCR-RV; immunological methods: a research of subpopulation of blood lymphocytes (method of a flow cytometry), determination of the spontaneous and induced products of IFNα and IFNγ, levels of serum cytokines and immunoglobulins (IL-1β, IL-6, IL-17, TNFα and IFNα and IFNγ, Ig A, M, G) by ELISA. The study was approved by the ethics board and informed consent was obtained from all patients.Results: Integral formulas of disorders in the antiviral immune defense system were created, which made it possible to isolate 3 pathological immunophenotypes (PIF): PIF1: NG↓+ind.IFNα/IFNγ↓+CTL↓+EKK↓+IgM↑+hypecytokinemiya (IL-1β↑+IL-6↑+TNFα↑); PIF2: NG↓+ ind. IFNα/IFNγ↓ + EKK↓+ IgG↓+hypercytokinemiya (IL-1β↑+IL-6↑+TNFα↑) and PIF3: NG↓+ind.IFNα/IFNγ↓+hypercytokinemiya (IL-1β↑+IL- 6↑+TNFα↑). Taking into account the identified disorders, a program of targeted interferon and immunomodulatory therapy was developed for each PIF: local and systemic IFN therapy + hexapeptide was developed for PIF1; for PIF2- local and systemic IFN therapy + glucosaminimuramyldipeptide; for PIF3-local and systemic IFN therapy.Conclusions: High clinical efficacy was demonstrated in 100% of patients with three groups of ACA-HVI. Immunological effectiveness of targeted interferon and immunomodulatory therapy programs: 89.5% for PIF1; for PIF2-57.6% and for PIF3- 37.5% of cases.

The review presents modern ideas about changes in the quantitative and qualitative composition of the human intestinal microbiome and their role in the development of stress-induced mental and neurological disorders, eating disorders, autism, etc. The dualism of the role of the commensal representatives of the microbiome, which have the ability to modulate metabolic and signaling reactions in conditionally healthy people and patients suffering from various neurological, psychoemotional and cognitive disorders associated with the development of neuroinflammation, is shown. The favorable and negative effects established by foreign researchers are associated with the presence of specific surface membrane proteins in the intestinal microbiota, the production of certain short-chain fatty acids, mucin degradation, changes in the intestinal barrier function, endotoxin production, as well as the synthesis of certain neurotransmitters. The prospects and difficulties of searching for new microbial biomarkers for predicting the development of stress-induced diseases, as well as for creating new microbial nutraceuticals and new-generation medicines based on living bacteria are considered.