Immunoglobulin Class Research Articles

Особенности течения COVID-19 у больных с хроническими вирусными гепатитами

Objective. To study the features of clinical picture and levels of proinflammatory cytokines (interleukin-1 and -6) and tumor necrosis factor-alpha in COVID-19 patients with CVH. Patients and Methods. A prospective case-control study included 222 patients admitted between 2020 and 2024 with a diagnosis of COVID-19 presenting with CVH at Zangiota Multidisciplinary Infectious Disease Clinic No. 1. The diagnosis of COVID-19 in all patients was verified either by polymerase chain reaction revealing SARS-CoV-2 ribonucleic acid (nasopharyngeal swabs) or by specific immunoglobulins of class M to coronavirus detected by enzyme immunoassay. The severity of the course of the disease was determined in accordance with the temporary methodological recommendations of the Republic of Uzbekistan “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19 Group I included 103 (46.39%) patients with chronic viral hepatitis C (CVHC), Group II included 104 (46.85%) patients with chronic viral hepatitis B (CVHB), and Group III included 15(6.76%) patients with mixt-hepatitis. The examination included: history taking; clinical examination of patients; standard clinical and biochemical blood tests; multispiral computed tomography and/or lung radiography. Serum levels of TNF-alpha and interleukins (hereinafter referred to as IL) -1, and -6 were determined using diagnostic test systems manufactured by VECTOR-BEST LLC (Novosibirsk, Russia) according to the attached instructions. Statistical processing of the obtained results was performed using Statstica.12 program. Methods of descriptive and variation statistics were used; Fisher's criterion and Pearson's linear correlation coefficient were calculated. Differences were considered reliable at p < 0.05. Results. In groups I and II, the moderately severe form of COVID-19 was significantly (p < 0.05) redominant; in the whole sample, as well as in the moderately severe course of the disease, women were significantly (p < 0.05) predominant; 9 out of 10 patients who died were men. The later a patient was admitted to the hospital, the more often severe COVID-19 was diagnosed. In all groups, men were hospitalized significantly (p < 0.05) later than women. In 12(5,41%) patients the diagnosis of “CVH” was detected for the first time in hospital by ELISA method: in 11 cases – CVHC, in another 1 – CVHB. Thirtysix(16.21%) patients had diabetes mellitus, 17 of them had moderate COVID-19, and 19 had severe COVID-19. There was a significant (p < 0.05) predominance of type 2 diabetes mellitus in patients from group I (25.2% vs. 3.6:% in group II, and 13.3% in group III, respectively). In 26 patients with diabetes mellitus from group I, the level of IL-6 was significantly (p < 0.05) higher (59.45 ± 18.15 pg/mL, versus 30.61 ± 4.24 and 31.0 pg/mL for groups II and III, respectively). The level of C-reactive protein in the general group amounted to 41.21 ± 1.68 IU/mL; the dynamics of this index had a wave-like character, increasing with aggravation of the condition and decreasing with increasing saturation and decreasing intoxication syndrome. In 78 (35.13%) patients at hospital discharge the level of CRP remained elevated (24.03 ± 1.47 mg/L). Conclusion. Timely detection of disorders in the systems of cytokine regulation and hemostasis in patients with the combination of COVID-19 and CVH will allow increasing the effectiveness of treatment (hepatoprotectors, anticoagulants) both in hospital and in the rehabilitation period. Key words: COVID-19, diagnosis, proinflammatory cytokines, tumor necrosis factor-alpha, chronic viral hepatitis

Virus-specific humoral immune response in Bulgarian COVID-19 patients with varying disease severity.

Our study aimed to analyze virus-specific humoral immune responses in COVID-19 patients with varying disease severity. A total of 109 serum samples from 87 patients, symptomatic for COVID-19 were studied using anti-SARS-CoV-2 immunoassays detecting different classes of immunoglobulins. Clinical samples were divided into 2 groups - collected up to and more than 2 weeks post-onset of symptoms (PoS). In the first group, the highest percentage of positive samples was found for IgA class virus-specific antibodies (78.1%), followed by IgM (71.9%/59.4%) and IgG (56.3%/53.1%). In the second group, samples positive for virus-specific IgA class antibodies were also the most (97.7%) along with those positive for IgG. A total of 72 IgA and/or IgM and/or IgG positive samples were further tested for SARS-CoV-2 neutralizing antibodies (NAbs) - 89.1% and 100% of samples obtained up to and after 2 weeks PoS, respectively were positive. Serological test results were also analyzed depending on the severity of the disease - SARS-CoV-2 positive samples in mild forms of COVID-19 were fewer than in moderate and severe forms but this difference was not statistically significant. SARS-CoV-2 specific antibodies and a high virus neutralization capacity of these antibodies appear early PoS; Immunoglobulins of IgA class are of most significant diagnostic value for detection of SARS-CoV-2 infection; Timing of testing is the most important factor for positivity rate.

Using a solid-phase variant of enzyme immunoassay for the etiological diagnosis of endogenous uveitis

Enzyme-linked immunosorbent assay (ELISA) has traditionally been used to diagnose infectious diseases, including ophthalmic ones. As a rule, however, investigators are only focused on differentiated detection of specific immunoglobulins (Ig) of varied classes, despite the fact that ELISA is able to register a wider range of emerging immune responses.Our purpose is to assess the effectiveness of the solid-phase version of ELISA for the etiological diagnosis of endogenous uveitis.Material and methods. 107 patients (114 eyes) aged 19 to 83 (ave. 45.2 ± 2.8 yrs) with various clinical forms of endogenous uveitis were examined by the traditional ELISA method. Along with the detection of specific Ig, the avidity of IgG and “paired” sera were studied.Results. In the primary serological examination, specific IgG were found in almost all patients (to herpes simplex viruses in 100 %, and to cytomegaloviruses in 96,3 %). Specific IgM were revealed in 3.7 % of cases. Specific IgG to T. gondii were found in 44.9 % of the patients and in 2 people, IgM. Specific IgG to C. trachomatis were found in 23 patients, and in two cases, IgM. By studying the avidity of antibodies, etiology was additionally deciphered in 1.9 % of patients. The study of “paired” sera helped determine the etiology of the disease in another 16 people.Conclusion. An integral approach using all diagnostic capabilities of ELISA, in particular the differentiated definition of specific Ig of various classes and the avidity of specific IgG, as well as the study of “paired” sera, made it possible to significantly increase the diagnostic capabilities of ELISA. As a result, the etiology was deciphered in 26 patients (24,3 %).

Стан загального імунітету в породілей із гнійними ранами під час воєнних дій

Purpose - to study the immune status of women giving birth with an infection of an obstetric surgical wound in the conditions of war, which will make it possible to develop and implement a pathogenetically justified method of wound infection therapy in the postpartum period. Materials and methods. We studied the immune status of 66 women in labor with an infection of an obstetric surgical wound in the conditions of war from February 24, 2022 and compared it with the indicators of general immunity of 76 women in labor with an infection of an obstetric surgical wound in peacetime. The material for the study of general immunity was peripheral blood, which was taken from the moment of infection of the obstetric surgical wound. To assess the state of general immunity, the total number of T lymphocytes (CD3+), their immunoregulatory subpopulations - T helpers/inducers (CD4+) and T suppressors/killers (CD8+), the number of B lymphocytes (CD22+), NK cells (CD16+) were counted), the immunoregulatory index (CD4+/CD8+) was calculated, the concentration of circulating immune complexes and immunoglobulins of classes A, M, G, phagocytic index and phagocytic number were determined. Statistical data processing was carried out using the package of application programs Microsoft Excel 5.0 and using the standard version Statistica 8.0. The difference in indicators was considered statistically significant at Р<0.05. Results. In women in labor with purulent wounds under the conditions of war under stressful conditions, there is a greater suppression of systemic immunity than in women in labor with this pathology in peacetime, which was manifested by T lymphopenia (decrease in CD3+ by 1.4 times, decrease in the level of T cells with helper activity (CD4+) by 1.2 times, immunoregulatory index (Tx/Tc) by 1.3 times), a decrease in the number of B lymphocytes (CD22+) and NK cells (CD16+) by an average of 1.2 times, a decrease indicators of immunoglobulins of classes A, M, G by an average of 1.3 times, phagocytic index) and phagocytic number relatively by 1.3 and 1.6 times, which led to an increase in the level of circulating immune complexes by 1.1 times. The absence of a significant difference between indicators of general immunity in parturient women with purulent wounds of the perineum and anterior abdominal wall was confirmed, which confirms the established doctrine that wounds of different localizations heal according to general laws and the body, namely the immune system, reacts equally to the wound process of any localization. Conclusions. When prescribing the treatment of an infection of an obstetric surgical wound, do not take into account the localization of the wound, since wounds of different localizations heal according to general laws and the immune system reacts in the same way. In women in labor with purulent wounds in wartime conditions, under stress, there is more suppression of systemic immunity than in women in labor with an infection of an obstetric surgical wound in peacetime, which increases the development and spread of the purulent-inflammatory process, increases the risk of severe septic complications, which leads to the development and implementation of a pathogenetically justified method of therapy of obstetric surgical wound infection in wartime conditions. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Organization for laboratory diagnosis of SARS-COV-2 in the conditions of an anti-tuberculosis institution

Introduction. In connection with the spread of a new coronavirus infection COVID-19 since 2020, measures have been taken in the city of Moscow to widely diagnose the causative agent of COVID-19. A laboratory PCR department was opened in the State Budgetary Healthcare Institution «MNPC for the fight against tuberculosis of the DZM», taking into account the available material and human resources. Purpose of the study: To generalize the experience of organizing the laboratory service of an anti-tuberculosis institution in the city of Moscow during the spread of a new coronavirus infection. Results. Human and material resources have made it possible to maintain the quality and availability of laboratory diagnostics of biological material from patients receiving treatment at the Moscow Regional Research and Practical Center for Combating Tuberculosis, DZM, during the COVID-19 pandemic. In the period 2020-2022 in total, 90,102 studies of biological material (smears) were carried out by RT-PCR in order to detect COVID-19 RNA. Starting from June 2020 to the present, the PCR department of the KDL Clinic 2 has been studying the direct detection of Covid-19 RNA in biological material using molecular genetic methods based on reverse transcription and polymerase chain reaction (RT-PCR) and the identification of specific immunoglobulin classes IgM and IgG to coronavirus antigens in blood serum (plasma) by the method of immunochemiluminescent analysis (ICLA) of both persons receiving treatment at the State Budgetary Institution of Healthcare Center for Combating Tuberculosis Moscow, and employees.

Assessment of the reliability of serological monitoring results based on biobank materials

Aim. To evaluate the safety of immunoglobulins (Ig) of different classes (IgA, IgM, IgG, IgE) under conditions of long-term low-temperature storage of blood serum samples.Material and methods. The work used samples of blood serum from the collection of the Department of Epidemiology, examined by enzyme immunoassay for antibodies of classes IgA, IgM, IgG, IgE twice as follows: immediately upon receipt in the laboratory and after storage at a temperature of -70о C for 8 years.Results. After the storage of seropositive sera, the level of IgA antibodies did not change significantly (p=0,7). For the remaining classes of immunoglobulins (IgM, IgG, IgE), a small (not >15%) but significant decrease (p<0,05), most pronounced for IgE, was observed. It was shown that the higher the antibody level in the samples during the first study, the more it decreased after long-term storage (correlation at p<0,05). This did not lead to false negative results, which is due to the greater accuracy in measuring small values.Conclusion. Long-term low-temperature storage of serum samples in biobank conditions ensures the safety of antibodies of different classes and is the basis for the reliability of future studies.

Assessment of basic immunological parameters in children with seizure disorders during acute infection

Introduction and objective: The objective of the study was to assess basic immunological parameters in children presenting with seizure disorders during acute infection. Materials and methods: The study was conducted from 19 January 2017 to 5 December 2020 at the Department of Infectious Diseases and Child Neurology in Poznań, and involved 121 patients aged 5–188 months: 64 with febrile seizures and 11 with generalised epilepsy. The control group comprised 46 patients with delayed psychomotor and intellectual development, pervasive developmental disorders, and neurodeficits. A complete blood count with differential white cell count, inflammatory markers, immunoglobulin classes (IgG, IgA, IgM), and the aetiology of infection were analysed using standard laboratory methods in all the cases. Results: Lower IgG was found in the febrile seizures group, and lower IgA was observed in the simple febrile seizure group compared to the patients after epileptic seizures. Patients with first-time simple febrile seizures showed lower IgG levels than the control group. Patients with generalised epilepsy and human herpesvirus 6 (HHV-6) showed lower IgG than the non-infected subjects. Patients with first-time complex febrile seizures had the lowest lymphocyte count compared to the control group. The lowest neutrophil count and total leukocyte count were found in HHV-6-infected patients with simple febrile seizures compared to the non-infected patients. Conclusions: Monitoring basic haematological parameters and immunoglobulin levels is an effective strategy in the diagnosis of seizure disorders in children. Screening tests provide an initial quantitative assessment of humoral and cellular responses, as well as impaired phagocytosis.

The dynamics of the content of immunoglobulins in the blood serum of piglets according to the actions of immunostimulating agents

Inconsistency in housing and feeding conditions, production stress, a combination of environmental factors, and technological solutions reduce the protective properties of the animal body, which often leads to a decrease in their productive properties. The work aimed to investigate changes in indicators of the humoral protection factor, in particular, the quantitative composition of immunoglobulins M, G, and A in the body of young pigs under the influence of immunostimulating agents Globigen® Pig Doser and Globigen® Jump Start, which include specific Ig Y. To perform this task in the conditions of the private farm of FG PE "Glynyany Agro" of Lviv region, Zolochiv district, which uses a single-phase method of raising pigs, a study was conducted with the involvement of 36 piglets-analogues of crossbreeds of the Great White and Landrace breeds, which were formed into three groups of 12 animals each. Piglets of the control group were fed feed of a standard diet. The piglets of the first experimental group were orally administered 2 ml/g of Globigen®Pig Doser during the first three days after birth. Then, according to the technology, they consumed the feed prescribed in the diet. The piglets of the second experimental group were given Globigen®Jump Start, which was mixed with the feed of the basic ration in the amount of 2 kg per ton of feed and, starting from the age of 7 days, was fed to the piglets according to the technology. It was established that the use of immunostimulating agents was characterized by an increase in Ig G and Ig A in the blood serum of piglets in the most critical period of their lives. Thus, in the blood serum of 30-day-old piglets under the influence of Globigen® Pig Doser, with a high level of probability (Р < 0.01), an increase of this class of antibodies to the level of 13.47 mg/ml was detected, with the use of Globigen® Jump Start, this indicator reached the mark 12.51 mg/ml. Since this period, colostral immunity, represented by placental immunoglobulins of class G and colostrum immunoglobulins of class A, is already exhausted; we assume that the formation of the body's immune response of young pigs has begun. We believe that the increase in the content of class A immunoglobulins, most likely the secretory form of the piglets themselves, when using Globigen® Jump Start, which reached the mark of 1.48 mg/ml, indicates the formation of immune resistance mechanisms. The effectiveness, specificity, and mechanism of action of these agents is based on the ability of their components, particularly Ig Y, to bind to pathogens or their fragments, to neutralize and safely remove them from the body, which helps to increase the barrier function of the intestinal mucosa. The obtained research results confirm the practicality of using Globigen® Pig Doser and Globigen® Jump Start immunostimulants during single-phase rearing of piglets to increase the level of non-specific resistance and obtain healthy young animals with a high level of viability.

THE EFFECT OF GERMANIUM IN LIPOSOMAL EMULSION ON THE RATS HUMORAL IMMUNE SYSTEM

The article deals with the immunostimulating and immunomodeling role of germanium on the body of rats.
 The experimental animals (2 groups) were injected subcutaneously with a 0.1% solution of Germanium in liposomal emulsion at a dose of 2.0 cm3 for four consecutive days. Clinical studies were conducted according to the model of a simple clinical experiment in parallel groups of animals.
 As a result of the study, it was found that after administration of Germanium in liposomal emulsion in rats, the level of immunoglobulins of class A, M and G, respectively, increased by 43.0% (p<0.01), 70.0% (p<0.001) and 35.0% (p<0.05) compared to the control group, indicating an increase in the protective role of antibodies as a factor of humoral immunity, activation of the complement system.
 After administration of germanium in liposomal emulsion in rats, the content of circulating immune complexes increased by 20.0% (p<0.05), the content of sialic acids by 40.0% (p<0.01) and the concentration of medium weight molecules decreased by 23.0% (p<0.05) compared to the control group, which is one of the components of the immune response.

IImmunological parameters in patients with chronic opisthorchiasis bearing gene mutations associated with osteoporosis-predisposition

To identify the features of the immune system functioning in patients with chronic opisthorchiasis bearing mutations in loci associated with predisposition to developing osteoporosis, comprehensive studies of cellular and humoral arms were carried out. The state of the phagocytic system was assessed by assessing absorption, metabolic activity and reactive oxygen species formation to restore nitrosine tetrazolium (spontaneous and stimulated NBT test). The phenotype of lymphocytes was determined by flow cytometry. The humoral immune arm was evaluated by the number of immunoglobulin classes M, G, A and E. Differences in the functional state of various arms of the immune system were revealed. In patients with chronic opisthorchiasis in the presence of rs1544410 polymorphism of the gene encoding the intracellular vitamin D receptor, the relative number of T-helper cells is significantly lower than in the group with the normal allele. In the presence of rs1800012 polymorphism of the gene encoding the α1-chain of type I collagen, the absolute lymphocyte count is significantly higher, spontaneous and stimulated NBT test were lower, the number of DN-T lymphocytes is significantly lower (both in relative and absolute values). In the presence of the rs3736228 mutation of the gene encoding the transmembrane low-density lipoprotein receptor, the level of myeloperoxidase and the neutrophil stimulation index are lower, the absorption activity of neutrophils is higher. The presence of the rs2234693 mutation for estrogen receptor gene leads to significantly increased level of stimulated NBT test and IgG concentration. Thus, patients with chronic opisthorchiasis bearing mutations in the COL1 A1, LRP5, ESR1(rs2234693) genes, have altered both nonspecific innate reactions and parameters of the adaptive immune arm; mutation of the VDR gene solely affects adaptive immunity. Analysis of the results suggests that the presence of mutations associated with the development of osteoporosis has a modulating effect on the immune response in chronic opisthorchiasis invasion. The identification of polymorphic genes associated with metabolic disorders of bone tissue and the study of the immunological profile in patients with chronic opisthorchiasis invasion will allow to implement an individual approach in the treatment of such patients.

Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA.

MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells show that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidylcitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T cells; however, the role of PADs in B cells remains to be elucidated. An unbiased analysis of human lung citrullinome was conducted to identify citrullinated proteins that are enriched in several chronic lung diseases, including rheumatoid arthritis-associated interstitial lung disease (RA-ILD), chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis, compared to healthy controls. Mass spectrometry, site-specific mutagenesis, and western blotting were used to confirm the citrullination of candidate proteins. Their citrullination was suppressed by pharmacological inhibition or genetic ablation of PAD2 and the impact of their citrullination on the function and differentiation of human B cells was examined with enzyme-linked immunosorbent assay, flow cytometry, and co-immunoprecipitation. Citrullinated MZB1 was preferentially enriched in RA-ILD but not in other chronic lung diseases. MZB1 was a substrate of PAD2 and was citrullinated during the differentiation of human plasmablasts. Ablation or pharmacological inhibition of PAD2 in primary human B cells attenuated the secretion of IgM and IgA but not IgG or the differentiation of IgM or IgA-expressing plasmablasts, recapitulating the effect of ablating MZB1. Furthermore, the physical interaction between endogenous MZB1 and IgM/IgA was attenuated by pharmacological inhibition of PAD2. Our data confirm the function of MZB1 in primary human plasmablasts and suggest that PAD2 promotes IgM/IgA secretion by citrullinating MZB1, thereby contributing to the pathogenesis of rheumatoid arthritis and RA-ILD.

Identification of bacterial protease domains that cleave human IgM

Immunoglobulin-degrading proteases are secreted by pathogenic bacteria to weaken the host immune response, contributing to immune evasion mechanisms during an infection. Proteases specific to IgG and IgA immunoglobulin classes have previously been identified and characterized, and only a single report exists on a porcine specific IgM-degrading enzyme. It is unclear whether human pathogens also produce enzymes that can break down human IgM. Here, we have identified four novel IgM-degrading proteases from different genera of human-infecting bacterial pathogens. All four protease domains cleave human IgM at a conserved and unique site in the constant region of IgM. These human IgM proteases may be a useful biochemical tool for the study of early immune responses and have therapeutic potential in IgM-mediated disease.

Natural resistance and immunological response of young Volyn meat breed to the action of probiotics

To investigate the response of natural resistance and immunological reactions of newborn young animals of the Volyn beef breed to the use of probiotic preparations. To conduct experimental research, three groups were formed from young Volyn meat breeds: the control group was fed only on mother's milk, the first group received a probiotic preparation with Bacillus Subtilis strain in addition to cow's milk, the second experimental group –– Lactobacillus spp. The activity of natural resistance and the body's immune response were studied on the 5th, 10th, and 30th day of the experiment. The level of nonspecific natural resistance was determined by indicators of bactericidal, lysozyme, phagocytic, and complementary activity of blood serum, and the immunological response was determined by the concentration of immunoglobulins of classes G, M, and A in the blood. It was established that starting from the 5th day of life, a difference in the nonspecific resistance of control and experimental animals was noted groups In separate age periods, probiotic supplements had a different degree of influence on the natural resistance of young animals. The greatest difference in the direction of growth in such indicators of non-specific resistance as bactericidal and complementary activity of blood serum was noted under the influence of the probiotic supplement Bacillus Subtilis (I experimental group), and indicators of lysozyme and phagocytic activity of blood serum were greater under the action of Lactobacillus spp. (II experimental group). The difference between indicators of bactericidal activity of blood under the action of Lactobacillus spp. in comparison with the control was at the age of 30 days (16.85 %, Р<0.01), and under the action of Bacillus Subtilis –– at the age of 60 days (25.49 %, Р<0.001). The level of phagocytic and complementary blood activity was the highest at the age of 60 days in the I experimental group –– by 17.17 % (Р<0.001) and 32.57 % (Р<0.001), in the II experimental group –– by 23.20 % (Р <0.001) and 36.34 % (Р<0.001), respectively. Regarding the concentration of immunoglobulins, the largest changes in their indicators were noted in the group that received Lactobacillus spp. Addition of probiotic strains of bacteria to the diet of young animals has a positive effect on the natural resistance and immune response of the body, which in the future will contribute to reducing the level of morbidity in young animals. Key words: calves, probiotics, bacterial strains, microorganisms, immunoglobulins, non-specific resistance of the organism, T-lymphocytes, phagocytic activity, bactericidal activity of blood serum.

PROBLEMS OF IMMUNOPREVENTION IN INDUSTRIAL POULTRY FARMING

The paper puts forward the concept that the use of the phenomena of immunological resonance and the vaccine function of pathogenic bacteria inactivated by an antibiotic multiple time increases the effectiveness of immunoprophylactic measures in industrial poultry farming. The timing of revaccinations has been established to ensure synchronization of the immunogenic action of the vaccine antigen and anti-idiotypes of immunoglobulins of different classes. The concept is put forward that pinocytosis occurring in the epithelial cells of the small intestine should be considered as non-specific phagocytosis, which increases the overall anti-infective resistance.

Designing Anti-Viral Vaccines that Harness Intrastructural Help from Prior BCG Vaccination.

Vaccines are among the most effective tools for combatting the impact and spread of infectious diseases. However, the effectiveness of a vaccine can be diminished by vaccine inequality, particularly during severe outbreaks of infectious diseases in resource-poor areas. As seen in many developing countries that lack adequate healthcare infrastructure and economic resources, the acquisition and distribution of potentially life-saving vaccines may be limited, leading to prolonged suffering and increased deaths. To improve vaccine equity, vaccine design must take into consideration the logistics needed to implement a successful vaccination drive, particularly among the most vulnerable populations. In the manuscript titled "Exploiting Pre-Existing CD4+ T Cell Help from Bacille Calmette-Guérin Vaccination to Improve Antiviral Antibody Responses" published in the Journal of Immunology, the authors designed a recombinant subunit vaccine against the Ebola virus (EBOV) glycoprotein that can harness the pre-existing T helper cells from prior BCG vaccination. As a recombinant subunit vaccine adjuvanted with alum, this approach has many features that make it well suited for the design of vaccines for developing nations, such as relative ease of production, scalability, and distribution. In addition, the high prevalence of BCG immunization and natural immunity to mycobacteria in many regions of the world endow such vaccines with features that should increase potency and efficacy among populations residing in such regions. As a result of using the helper activity of pre-existing BCG-specific Th cells to drive antibody responses, a lower vaccine dose is needed, which is a major advantage for vaccine manufacture. Furthermore, the BCG-specific Th cells also stimulate immunoglobulin class switching to IgG isotypes that have strong affinities for activating Fc-gamma receptors (FcγRs). Taken together, we propose that the design of subunit vaccines with intrastructural help from BCG-specific Th cells can improve protection against viral infection and represents a vaccine design that can be generally adapted to other emerging viral pathogens for the control and prevention of infection in many developing countries.

Effect of platelet automesoconcentrate on the immunological status of experimental animals after liver resection

Objective. To study the indices of cellular and humoral immunity in the blood of rats after liver resection and under conditions of administration of platelet automeso–concentrate.
 Materials and methods. The study was performed on albino Wistar rats weighing 140 – 245 g. Resection of 2/3 of the liver was performed using the method of aseptic removal of its left and central lobes. During the resection, platelet autologous concentrate at a dose of 1 ml/kg was injected into the liver residue. To characterise the cellular and humoral components of immunity, the levels of leukocytes, lymphocytes, the number of total T– and B–lymphocytes, the level of circulating immune complexes, and the content of immunoglobulins of classes G and M were determined.
 Results. In the initial stages after liver resection, a marked leukocytosis was observed, accompanied by an increase in the relative number of basophils, eosinophils, rods and monocytes and a decrease in the level of segmented neutrophils and lymphocytes. The level of lymphocytes decreased at the expense of the T–cell population. Against the background of an increase in the number of B–lymphocytes, there was an increase in the levels of immunoglobulins M, G and circulating immune complexes. The injection of platelet autologous concentrate into the liver residue during resection of this organ stimulated the cellular and humoral immunity, as the studied parameters were higher than those of animals that did not receive platelet autologous concentrate. On the 7th day after partial hepatectomy, the studied parameters approached the control values.
 Conclusions. Components of cellular and humoral immunity can directly or indirectly affect the processes of liver regeneration after liver resection. B–cells after liver resection as antigen–presenting cells can trigger and modulate the immune response, which is enhanced by the introduction of platelet autologous concentrate into the body.

Newly identified common variable immunodeficiency in an elderly patient with rheumatoid arthritis

Common variable immunodeficiency is a group of heterogeneous diseases that are primary immunodeficiencies with a predominant lack of antibody synthesis. The most common manifestation is chronic infectious pathology of the respiratory tract, less often of the gastrointestinal tract, as well as septic arthritis. Non-infectious manifestations include autoimmune diseases, non-infectious diarrhea, cancer, benign lymphoid hyperplasia. In one patient, a combination of several syndromes is possible. Unlike most other primary immunodeficiencies that debut in early childhood, this pathology often manifests in the third or fourth decade of life, and sometimes later in apparently healthy people. Although the routine laboratory method for determining the concentration of the main classes of immunoglobulins makes it quite easy to identify patients with common variable immunodeficiency, often the diagnosis is made many years after the onset of the first clinical symptoms, when serious complications have already developed. The disease is characterized by a gradual onset, chronic progressive course and ineffectiveness of standard therapy. The main method of treatment is lifelong replacement therapy with intravenous immunoglobulins. The article considers a clinical case when an elderly patient with seronegative rheumatoid arthritis with a juvenile onset was diagnosed many years later. The results of immunological studies, including immunophenotyping of peripheral blood and bone marrow lymphocytes, are presented. Issues of differential diagnosis with secondary hypogammaglobulinemia and lymphoproliferative diseases are highlighted. It has been stated that until now, doctors of various specialties are not sufficiently familiar with the problem of primary immunodeficiencies, especially when it comes to adults, and non-infectious manifestations dominate in the clinical picture.

Vitamin A and vitamin D induced nuclear hormone receptor activation and its impact on B cell differentiation and immunoglobulin production

Vitamin A and vitamin D metabolites are ligands to nuclear receptors – namely RAR, RXR and VDR. The activation of these receptors in human B cells impacts B cell maturation and function. In this review, we discuss how 9-cis retinoic acid (9cRA) and 1,25-dihydroxyvitamin D3 (calcitriol) individually or in conjunction, signal through their nuclear receptors and thereby impact B cell differentiation, immunoglobulin class switching to IgA at the expense of IgE, and also B cell migration and homing. Impact of the vitamin metabolites individually on B cell survival factors are well elucidated, be it the regulation of BAFF and APRIL, the induction of TGF-β or suppression of NF-κB. Very little is known about the impact of 9cRA and calcitriol together on B cells. Recently our group revealed that 9cRA and calcitriol together in the context of the B cell differentiation, induces naïve B cell differentiation into IgA+ plasmablasts, the functional and underlying molecular regulations however require further investigation. In conclusion, the conjunctional impact of these nuclear receptor ligands on B cell functionality is important to better understand B cell dependent clinical outcomes in allergy and autoimmunity. Within this review, we hypothesize that a balance between both vitamins is of utmost importance to provide a robust humoral immune response and a better treatment of disorders characterised by dysregulated immune responses such as IgE-dependent allergy or autoimmunity such as lupus erythematosus.

Associations between Antiepileptic Use and Hypogammaglobulinaemia: Findings from a Population-Based Case-Control Study Using Data Linkage

Background and Objectives: Increased mortality in epilepsy due to infections (other than pneumonia) has been demonstrated. Small case series of people on antiepileptic drugs (AEDs) have described hypogammaglobulinaemia, which may predispose to infections. It is unclear whether hypogammaglobulinaemia is more frequent in people on AEDs, what AEDs it is associated with, or what clinical impact it has. In this population-based study, we aimed to determine whether AEDs were associated with hypogammaglobulinaemia, which AEDs were associated, and whether the associations may be causal. Methods: We conducted an unmatched case-control study using data linkage of routinely collected biochemistry, prescribing, and morbidity datasets in North-East Scotland from 2009–2021. Cases were participants with immunoglobulin levels less than the reference range. Controls were those with normal/high immunoglobulin levels. Logistic regression was used to investigate associations between AED exposure and any hypogammaglobulinaemia, adjusting for age, sex, and comorbidity. We also analysed low IgA, IgM, and IgG separately. We analysed “any AED” exposure and common individual drugs separately. Cumulative exposure data were used to determine whether an exposure-response relationship was present. Results: 18,666 cases and 127,157 controls were identified. Use of any AED was associated with increased risk of hypogammaglobulinaemia (adjusted odds ratio [aOR] 1.20 [95% CI: 1.15–1.25]). Phenytoin use was strongly associated with low IgA (aOR 5.90 [95% CI: 3.04, 10.43]). Carbamazepine and lamotrigine were also associated with low IgA. Apart from topiramate, which was associated with a non-significant decrease in odds of hypogammaglobulinaemia, there was a consistent increase in odds of hypogammaglobulinaemia across most AEDs studied. Panhypogammaglobulinaemia was associated with any AED use, carbamazepine, lamotrigine, gabapentin, and multiple AED use. There was evidence of an exposure-response relationship between any AED use and any hypogammaglobulinaemia, low IgA, and low IgG. Carbamazepine and probably lamotrigine also had an exposure-response relationship with any hypogammaglobulinaemia. Discussion: AEDs may increase hypogammaglobulinaemia risk. Specific classes of immunoglobulins are differentially affected, and the exposure-response analysis suggests this may be causal. Further work should investigate the clinical impact of these findings. Clinicians should check immunoglobulin levels if unusual or recurrent infections occur in patients treated with AEDs.

Determination of optimum nanofiltration conditions for the manufacturing process of human normal immunoglobulin G for intravenous administration

Scientific relevance. Medicinal products based on immunoglobulin class G (IgG) from human plasma are widely used in clinical practice to treat bacterial and viral infections, primary and secondary immunodeficiencies, and autoimmune diseases. Nanofiltration is a way to mitigate the risk of in-process contamination of raw materials with various pathogens, including viruses. Therefore, it is relevant to investigate the development and implementation of additional viral inactivation and/or elimination steps.Aim. This study aimed to develop and validate optimum nanofiltration conditions and to scale up the nanofiltration step for the manufacturing of human IgG for intravenous administration.Materials and methods. The study used a solution of IgG from plasma fractions II and III. The authors paired nanofilters manufactured by Planova 20N and BioEx (Asahi Kasei, Japan), Viresolve Pro (Merck Millipore, USA), Virosart HC and HF (Sartorius, Germany), and Pegasus SV4 and Prime (Pall, USA) with Sartopore polyethersulphone prefilters by Sartorius (Germany), Virosart MAX polyamide prefilters by Sartorius (Germany), and EKX-P regenerated cellulose prefilters by Pall (Germany). Virus reduction validation studies were performed with model viruses (human immunodeficiency virus type 1, porcine transmissible gastroenteritis virus, porcine parvovirus, murine encephalomyocarditis virus, and bovine viral diarrhoea virus) in the laboratories of the N.F. Gamaleya centre. The sample data analysis involved calculating mean values with 95% confidence intervals.Results. For all the selected combinations of prefilters and filters, the maximum nanofiltration throughput depended on the IgG concentration in the test solution. With the combination of an EKX-P filter with a Pegasus SV4 nanofilter, the maximum throughput and the IgG yield reached 6300 g/m2 and 95%, respectively. When combined with a Planova 20N nanofilter, EKX-P and Sartopore (polyethersulphone) filters provided a maximum throughput of up to 2980 g/m2 and an IgG yield of almost 100%, provided that the test solution had an IgG concentration of 10 g/L. With different filter combinations, virus reduction levels ranged from 4.00±0.05 to 4.75±0.04 log10 for human immunodeficiency virus type 1, from 4.30±0.04 to 4.55±0.06 log10 for porcine transmissible gastroenteritis virus, from 5.38±0.08 log10 to 5.57±0.04 log10 for murine encephalomyocarditis virus, 5.12±0.10 log10 to 5.25±0.08 log10 for porcine parvovirus, and exceeded 5.00 log10 for bovine viral diarrhoea virus. The virus reduction levels achieved were not statistically associated with prefilter brands.Conclusions. The study demonstrated that nanofiltration was effective at removing viruses with various virion sizes and physicochemical characteristics, including viruses as small as parvovirus B19. The levels of virus reduction exceeded 4 log10 and met the acceptance criteria.The laboratory-scale nanofiltration parameters and the corresponding filtration times, as well as IgG yields, did not change when the process was scaled up. Therefore, nanofiltration is an effective and productive technique that helps eliminate various types of viruses and considerably improve viral safety without affecting the quality of biological medicinal products.