Aim. To investigate the types of immune response regulation and immunological tolerance disorders in autoimmune diseases.
Methods. Bibliometric indicators` analysis of scientific articles and analytical materials from databases such as Scopus, Web of Science, DOAJ, and PubMed were used.
Results. The most important types of regulation of the immune response, which are disturbed in autoimmune diseases, are the withdrawal of immunological tolerance to self-antigens (in which cellular and cytokine types of regulation become unbalanced) and genetic type. It analyzed the consequences of dysregulation of cellular, cytokine, genetic, idiotypic-anti-idiotypic, and immuneneuroendocrine types, which cause a breakage of immunological tolerance and the start of autoaggression.
Conclusions. The consequences of dysregulation of the immune response, which causes the reversal of immunological tolerance, create the ground on which numerous autoimmune reactions quickly form into an autoimmune syndrome and become autoimmune diseases.
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.
Before the implementation of newborn screening (NBS), only a few cases of agammaglobulinemia associated with IGLL1 variants had been reported. The IGLL1 gene encodes the surrogate light chain components λ5 and VpreB, which form a crucial part of the pre-B cell receptor complex. A recently published study reported 17 cases of agammaglobulinemia caused by IGLL1 variants, the vast majority of which were identified through NBS. Here, we report two cases of B-cell lymphopenia along with IGLL1 variants identified through NBS in Ukraine. Both neonates had undetectable KREC and normal TREC levels at birth. Despite the presence of B-cell lymphopenia, only one patient exhibited a transient decline in IgG levels. IgA and IgM levels remained normal during the first year of follow-up, which had not been reported in previous IGLL1 cases. Both children presented with mild upper respiratory tract infections. Genetic analysis revealed that both patients carried the c.425C > T variant, with one patient also harboring the c.258del variant. These variants have been linked to B-cell lymphopenia and low KREC levels in prior studies. Two additional variants were identified on the second chromosome: c.368C > G, which is predicted to be tolerated, and c.377T > C, which is likely disruptive. This study highlights the potential underdiagnosis of B-cell lymphopenia caused by IGLL1 variants. Moreover, the comparison between clinically diagnosed cases and those identified through NBS underscores the importance of early diagnosis that facilitates close monitoring of affected patients from birth, timely initiation of immunoglobulin replacement therapy, and the prevention of complications and severe manifestations.
Keywords: B-cell lymphopenia; IGLL1 gene; KREC; autosomal-recessive agammaglobulinemia; diagnosis; inborn errors of immunity; newborn screening.
From December 13 to 15, 2023, the International Medical Forum (IMF) “Ukrainian and Global Medicine: Basics, Reality, and Strategic Prospects” was held successfully. Within the framework of this forum, the 12th Christmas Readings on Immunology and Allergology were held. The event was dedicated to the 150th anniversary of the Shevchenko Scientific Society (SSS), the 125th anniversary of the Medical Commission of the SSS, and the 25th anniversary of the Department and Center of Clinical Immunology and Allergology. Event hosts were the Medical Commission of the Shevchenko Scientific Society and Danylo Halytsky Lviv National Medical University. Despite difficult times for Ukraine, the event did not lose its leadership positions in terms of the number of speeches and the diversity of the agenda, and the vast geography of speakers and specialist attendees distinguished it. More than 400 speakers, about 1,000 listeners, and more than 1,200 online participants participated in the event. During three days, international experts from the USA, Canada, UK, Italy, Spain, Denmark, Slovakia, Sweden, Germany, Austria, and Poland, and leading scientists and experts for Ukraine delivered more than 300 speeches.
У період з 13б по 15 грудня 2023 року з великим успіхом відбувся ювілейний Міжнародний медичний форум (ММФ) «Медицина України та світу: основи, реалії та стратегічні перспективи», в рамках якого пройшли традиційні ХІІ “Різдвяні читання з імунології та алергології”[1] . Захід був присвячений 150-
річчю Наукового Товариства ім. Шевченка (НТШ), 125-річчю Лікарської комісіїНТШ та 25-річчю кафедри та центру клінічної імунології та алергології [2]. Організаторами події виступили Лікарська комісія НТШ та Львівс
ький національний медичний університет ім. Данила Галицького. Незважаючи на складні часи для України,
захід не втратив своїх лідерських позицій за кількістю доповідей, насиченістю програми, а також відзначився
широкою географією спікерів та відвідувачів - спеціалістів. Загалом в події взяли участь понад 400 спікерів,
близько 1000 слухачів та понад 1200 онлайн -учасників. Впродовж трьох днів міжнародними експертами
США, Канади, Великобританії, Італії, Іспанії, Данії, Словаччини, Швеції, Німеччини, Австрії, Польщі, а
також провідними вченими та експертами України було прочитано понад 300 доповідей.
Ключові слова: Міжнародний Медичний Форум, Медицина України та світу, ХІІ “Різдвяні читання з імунології та алергології
In early July 2024, a prominent Ukrainian scientist, educator and historian of medicine, Professor Yaroslav Volodymyrovych Ganitkevych, celebrated his 95th birthday. A Doctor of Medicine, a full member of the Shevchenko Scientific Society (SSS) and an honorary member of the Ukrainian Medical Society (UMS), he left a memorable mark in Ukrainian medicine. His numerous works on the history of medicine, scientific heritage, and active work in medical
education have become significant assets for science and society.
Keywords: Yaroslav Ganitkevych, history of medicine, Shevchenko Scientific Society (SSS),
SSS Medical Commission