Abstract
Advanced glycation end products (AGEs), and particularly the unique AGE10 epitope, may be a potential biomarker
of immunopathology in rheumatic diseases. They may be associated with inflammation, joint damage and ossification processes. AGE10 present in human and animal tissues could be detected with monoclonal antibody against melibiosederived glycation product MAGE synthesized in anhydrous conditions. This MAGE product was different from the classic synthesis in water solution. The epitope was determined in serum with ELISA using these anti-MAGE monoclonal antibodies. This work aims to determine serum AGE10 levels in patients with reactive arthritis (ReA)-caused with Chlamydia trachomatis (group 2) and ReA with C. trachomatis during the reactivation of EBV infection (group 3). Additionally, ankylosing spondylitis (AS) patients (group 4) were involved in the study, due to the potential evolution of ReA toward AS. The control group maintained physiological AGE10 levels (316 μg/ml), while the combined infection group showed elevated AGE10 (850 μg/ml) compared to the chlamydial-only group (17 μg/ml). Fluorescent fAGE were at the highest level in AS patients. A striking finding was the complete absence of detectable AGE10 antigen in the AS group, coinciding with notably elevated immune complex AGE10–anti-AGE10 levels. A similar pattern was observed in patients with ReA caused by C. trachomatis alone (Group 2), albeit to a lesser extent. In contrast, both the control group and patients with ReA associated with EBV coinfection (group 3) displayed an inverse relationship, characterized by higher antigen levels and lower immune complex concentrations. Thus, diminished level of AGE10 could be caused, besides local accumulation,
also by immune complexes formation, a pathogenic factor. Therefore, evaluating disease activity in ReA and AS is
crucial to further our understanding of the pathophysiology of AGEs formation and predicting prognosis.
Keywords Advanced glycation end products (AGEs) · AGE10 · Reactive arthritis · Ankylosing spondylitis · Chlamydia
trachomatis · Epstein–Barr virus · Immune complexes · Oxidative stress

УДК: 616.891.6-06:616-001]-36-092:612.017

Посттравматичний стресовий розлад (ПТСР) є психіатричною патологією і важливою проблемою для стану здоров’я людини, що розвивається внаслідок травматичної події. На сьогоднішній день в Україні проблема ПТСР є дуже гострою. Повномасштабна війна і події, пов’язані з пандемією SARS-CoV 2, значною мірою вплинули на життя і психічний стан українців. У статті наведені дані з іноземних і вітчизняних фахових літературних джерел щодо причин формування ПТСР, особливостей його перебігу, в т.ч. залежно від статі, та наслідків для здоров’я людини. Акцентується увага на змінах у роботі клітинної та гуморальної ланок природженої та адаптивної імунної відповіді. Розкриваються імунопатологічні механізми формування захворювань різних органів і систем на тлі ПТСР. Продемонстровано, що ПТСР руйнує гомеостаз організму, а саме взаємодію між ендокринною, нервовою та імунною системами. Показано, що головними наслідками впливу тривалого ПТСР на ключову систему гомеостазу людини – імунну, є формування імунопатології – імунодефіцитів та автоімунних хвороб.

УДК: 616.5-002.2-056.25-053.2:613.221]-07:616.017

Introduction. It is now known that 30% of patients who have recovered from COVID-19 develop long-COVID. According to researchers, the reactivation of herpesviruses plays a significant role in triggering long-COVID. In these patients, alteration in lymphocyte populations and T-lymphocyte subpopulations have been observed, yet the nature of these changes remains unclear. The dysregulation of the immune response caused by SARS-CoV-2 is further exacerbated by the reactivation of human herpesvirus type 6 (HHV-6). Therefore, it is essential to distinguish immune response alterations in long-COVID patients based on HHV-6 reactivation and consider these differences when developing therapeutic approaches.

The aims of this study were: 1) to investigate the associative relationships between the number of lymphocyte populations, T-lymphocyte subpopulations, and the severity of the clinical course of COVID-19 in patients with long-COVID; 2) to determine and compare the percentages of CD3+, CD4+, CD56+, CD8+, CD4/25/127– T-regs and CD19+ cells in long-COVID patients depending on the presence of reactivated HHV-6.

Materials and methods. In our study, we examined 124 patients, including 73 women (59%) and 51 men (41%), with an average age of 43±9.70 years, all of whom had suffered from COVID-19 in the second half of 2023. To confirm HHV-6 reactivation and form study groups, molecular genetic studies (PCR) were conducted on all patients. Subsequently, flow cytometry was used to analyze the lymphocyte populations and subpopulations in peripheral blood samples from the patients.

Results. In patients with long-COVID following severe COVID-19, the percentage of CD3+ T cells, CD8+ cells, and CD4+CD25+CD127– T-regs was significantly lower both in the absence of HHV-6 reactivation (p=0.014; p=0.016; p=0.045, respectively) and during the active phase of HHV-6 reactivation (p=0.045; p=0.005; p=0.008, respectively), compared to the control group. CD4+ T cells were significantly decreased only during the active phase of the herpesvirus (p=0.045). Notably, in the active phase of HHV-6, these cells were further reduced compared to those without herpesvirus reactivation. Additionally, the number of CD19+ B cells was significantly elevated in patients with HHV-6 reactivation, compared to both the control group (p<0.0001) and patients without HHV-6 reactivation (p=0.0002). Furthermore, the percentage of CD56+ NK cells in patients with long- COVID following mild and moderate COVID-19 in the history, without HHV-6 reactivation, did not differ significantly from the control group. However, NK cells were significantly lower in patients with long-COVID after severe COVID-19 in the context of HHV-6 reactivation (p=0.0001).

Conclusions. Our data confirm that HHV-6 reactivation after COVID-19 plays a role in the development of long-COVID. This is mediated through dysregulation of adaptive immune cell interactions, activation of the NF-κB signaling pathway, and increased production of antibodies with defective structure. Based on our results, patients with long- COVID following severe COVID-19, in the context of HHV-6 reactivation, may have an elevated risk of immunopathological complications, potentially including autoimmune disorders. These findings offer valuable insights for future research and potential therapeutic strategies.

Introduction: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. Although RA is chiefly associated with HLA class II, nevertheless some HLA class I associations have also been observed. These molecules present antigenic peptides to CD8+ T lymphocytes and natural killer cells. HLA-I molecules bind their peptide cargo (8–10 amino acids long) in the endoplasmic reticulum. Peptides longer than 10 amino acids are trimmed by the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 to fit the peptide binding groove of the HLA-I molecule. Here, we investigated the possible association of ERAP1 and ERAP2 polymorphisms with RA, and also any possible correlation between serum levels of the ERAP2 protein with disease severity.

Methods: We used Real-Time PCR to genotype ERAP1 and ERAP2 and ELISA test to detect ERAP2 protein.

Results: We found significant associations of ERAP1 rs30187, rs27044, and rs26618, as well as ERAP2 rs2248374, with susceptibility to RA. ERAP1 rs26653 and ERAP2 rs2248374 were also associated with the Disease Activity Score (DAS28), and some polymorphisms were also associated with anti-citrullinated protein or anti-mutated citrullinated vimentin antibodies. RA patients secreted higher concentrations of ERAP2 than controls. Patients with mild disease activity (DAS28 < 3.2) released a concentration of ERAP2 four times lower than that of patients with severe disease activity (DAS28 > 5.1). We detected a higher level of ERAP2 in rheumatoid factor (RF)-positive patients than in RF-negative patients. ERAP2 concentration above 5.85 ng/mL indicated a severe phase of RA.

Conclusions: Some ERAP1 and ERAP2 polymorphisms seem to be related to susceptibility to RA or the severity of the disease. The ERAP2 protein tested in serum could be a valuable biomarker of RA severity.