Immunoglobulin Class Research Articles

High levels of immunoglobulin expression predict shorter overall survival in patients with acute myeloid leukemia.

It has been believed that immunoglobulins can only be produced by B lymphocytes and plasma cells. We have previously reported that IgG can be expressed in myeloblasts from patients with acute myeloid leukemia (AML) and plays a role in the proliferation and apoptosis of leukemic cells. However, its clinical impact has not been assessed. We assessed the expression of different classes of immunoglobulin in peripheral blood and bone marrow samples from 132 AML patients and correlated the levels of expression with clinicopathologic and molecular genetic features, as well as clinical outcome. We found that, in addition to IgG, all classes of immunoglobulin are expressed in myeloblasts, including IgG, IgM, IgA, IgD, IgE, Igκ, and Igλ. The levels of IgG expression (coupled with Igκ or Igλ) are higher than those of IgM, IgA, IgD, and IgE. Using receiver operating characteristic (ROC) curve analysis, we identified two distinct groups of AML patients with differential expression of immunoglobulin and different clinical outcomes. High levels of immunoglobulin expression are associated with monocytic differentiation, multilineage dysplasia, TET2 and KRAS mutations, and poor overall survival. Assessment of immunoglobulin may serve as a useful marker for prognostic stratification and target therapy.

Prognostic implications of the expression levels of different immunoglobulin heavy chain-encoding RNAs in early breast cancer

The extent and composition of the immune response in a breast cancer is one important prognostic factor for the disease. The aim of the current work was to refine the analysis of the humoral component of an immune response in breast tumors by quantifying mRNA expression of different immunoglobulin classes and study their association with prognosis. We used RNA-Seq data from two local population-based breast cancer cohorts to determine the expression of IGJ and immunoglobulin heavy (IGH) chain-encoding RNAs. The association with prognosis was investigated and public data sets were used to corroborate the findings. Except for IGHE and IGHD, mRNAs encoding heavy chains were generally detected at substantial levels and correlated with other immune-related genes. High IGHG1 mRNA was associated with factors related to poor prognosis such as estrogen receptor negativity, HER2 amplification, and high grade, whereas high IGHA2 mRNA levels were primarily associated with lower age at diagnosis. High IGHA2 and IGJ mRNA levels were associated with a more favorable prognosis both in univariable and multivariable Cox models. When adjusting for other prognostic factors, high IGHG1 mRNA levels were positively associated with improved prognosis. To our knowledge, these results are the first to demonstrate that expression of individual Ig class types has prognostic implications in breast cancer.

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Objective To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19). Design Systematic review and meta-analysis. Data sources Medline, bioRxiv, and medRxiv from 1 January to 30 April...

Clinical and laboratory characteristics of patients with common variable immune deficiency

Objective: to identify clinical and laboratory features of common variable immune deficiency (CVID) in different age groups of patients. Material and methods. The clinical and anamnestic characteristics of 36 patients (16 men and 20 women) aged 15 to 65 (the average age was 37.0±12.7) diagnosed with CVID were studied. Results. Among the examined patients the disease was manifested at the mature age in 25 people (69.4 %) - the 1st group, while in 11 people (30.5 %) the debut of the disease occurred during childhood (from 4 to 17) - the 2nd group. Among the patients of the first group, the greatest number of cases (10 cases, 40.0 %) was found at the age of 20-30; in the children's age group, the greatest number of cases (8 cases, 72.7%) occurred at the age of 13-17. Non-infectious manifestations were significantly more common in adult patients at the onset of the disease (64 %; χ2 = 15.68; p < 0.001). Infectious and inflammatory diseases of the ENT organs and respiratory tract were observed with the same frequency in both the groups. Children significantly more often than adults (72.7 %; χ2 = 26.6; p < 0.001) observed a deficit in the three classes of immunoglobulins (Ig) (IgA, IgM, and IgG), whereas in patients with CVID manifestation in adulthood, the concentrations of IgA and IgG were mainly reduced, and meanwhile the degree of the decrease in the immunoglobulin level was more pronounced (72.0 %; χ2 = 14.47; p < 0.001). Conclusion. Significant differences in the clinical and laboratory parameters of CVID manifestation in the patients depending on age have been revealed.

The recent advances in non-homologous end-joining through the lens of lymphocyte development

Lymphocyte development requires ordered assembly and subsequent modifications of the antigen receptor genes through V(D)J recombination and Immunoglobulin class switch recombination (CSR), respectively. While the programmed DNA cleavage events are initiated by lymphocyte-specific factors, the resulting DNA double-strand break (DSB) intermediates activate the ATM kinase-mediated DNA damage response (DDR) and rely on the ubiquitously expressed classical non-homologous end-joining (cNHEJ) pathway including the DNA-dependent protein kinase (DNA-PK), and, in the case of CSR, also the alternative end-joining (Alt-EJ) pathway, for repair. Correspondingly, patients and animal models with cNHEJ or DDR defects develop distinct types of immunodeficiency reflecting their specific DNA repair deficiency. The unique end-structure, sequence context, and cell cycle regulation of V(D)J recombination and CSR also provide a valuable platform to study the mechanisms of, and the interplay between, cNHEJ and DDR. Here, we compare and contrast the genetic consequences of DNA repair defects in V(D)J recombination and CSR with a focus on the newly discovered cNHEJ factors and the kinase-dependent structural roles of ATM and DNA-PK in animal models. Throughout, we try to highlight the pending questions and emerging differences that will extend our understanding of cNHEJ and DDR in the context of primary immunodeficiency and lymphoid malignancies.

Evaluation of Radiation Sensitivity in Patients with Hyper IgM Syndrome

ABSTRACT Background HIGM syndrome is a rare form of primary immunodeficiencies characterized by normal/increased amounts of serum IgM and decreased serum levels of other switched immunoglobulin classes. Since the affected patients are continuously infected with various types of pathogens and are susceptible for cancers, diagnostic and therapeutic tests including imaging techniques are recommended for the diagnosis and treatment of these patients, which predispose them to higher accumulated doses of radiation. Given the evidence of class switching recombination machinery defect and its association with an increased rate of DNA repair, we aimed to evaluate radiation sensitivity among a group of patients diagnosed with HIGM syndrome. Methods 19 HIGM patients (14 CD40 L and 3 AID deficiencies and 2 unsolved cases without known genetic defects) and 17 control subjects (10 healthy subjects as negative control group, 7 ataxia-telangiectasia patients as positive control group) were enrolled. G2 assay was carried out for the determination of radiosensitivity. Results Based on radiation-induced chromosomal changes among the studied HIGM patients and their comparison with the controls, almost all (95%) the patients had degrees of radiosensitivity: 6 patients with low to moderate, 1 patient with moderate, 11 patients with severe and 1 patient without radiation sensitivity. Conclusion Today, X-ray radiation plays a very important role in diagnostic and therapeutic procedures; while increased exposure has devastating effects especially in radiosensitive patients. Considering higher sensitivity in HIGM patients, utilizing radiation-free techniques could partly avoid unnecessary and high-level exposure to radiation, thus preventing or reducing its harmful effects on the affected patients.

Immunoglobulins and predicted mortality in clinical course of concomitant HIV and TB infection

A search for prognostic markers of HIV and tuberculosis coinfection (HIV/TB), especially in case of Mycobacterium tuberculosis multidrug resistance (MDR MBT) associated with low rates of TB eradication, is of relevance in connection with the problem of choosing adequate anti-TB therapy which is able to decrease mortality. 113 HIV/TB patients aged 24 to 58 years were examined: 70 males and 43 females hospitalized at the Novokuznetsk TB Clinic during the 2017—2019 period. MDR MBT (concomitant resistance to Isoniazid and Rifampicin) was found in 50 patients (12 patients with MDR MBT had additional resistance to Fluoroquinolones) aged 24 to 54 years — 31 males and 19 females. The control group consisted of 49 healthy individuals aged 27 to 72 years (26 females and 23 males) lacking focal and systemic infections with moderately pronounced age-related changes. In plasma samples, concentration of total (non-specific) immunoglobulins of classes E, M, G, A (including secretory immunoglobulin A, sIgA) were measured by using enzyme-linked immunosorbent assay. Data statistical processing was performed by using licensed software packages InStatII, Microsoft Excel, IBM SPSS Statistics 22. An extended range of individual variability in count of peripheral blood CD4 lymphocytes was revealed both among non-survivor and survivor patients with HIV/TB examined, being a drawback of using such parameter as lethality predictor. It was found that the serum level of total IgE, IgM, IgG, IgA and sIgA in patients with HIV/ TB was higher than that one in control group, whereas in non-survivor vs. survivor patients the concentration of IgE and sIgA was elevated. The coefficient of disease outcome prediction (CP) for patients with HIV/TB and MDR MBT was calculated being equal to the ratio of the multiplication of serum concentration of IgE, IgM, IgA and secretory IgA to CD4 lymphocyte count (CP = IgE x IgM x IgA x sIgA/CD4). CP higher than 200 was detected in 77% non-survivor and 6% of survivor patients. The relative risk of death with CP 200 was very high (OR = 56.7, p 0.0001) being 8.5 times higher than that one upon CD4 200 (OR = 6.7, p = 0.0237). A positive correlation between CP and lethal outcome was more valuable than that of CD4. The data presented allow us to propose CP for clinical use as an effective prognostic criterion for HIV/TB with MDR MBT.

Il deficit di IgA

IgA deficiency (D-IgA) in the paediatric population is often an occasional finding during tests performed for other reasons in children in whom an immunodeficiency disorder is not suspected. D-IgA is the most common primary immunodeficiency with a variable prevalence according to ethnicity, estimated on 1 case/600 in the Caucasian population. IgA should be dosed twice in a child > 4 years of age to confirm the deficiency, which is defined by the presence of serum IgA < 0.07 g/l. The other classes of immunoglobulins should always be dosed. Most patients with D-IgA will not require any treatment or follow-up (85% are asymptomatic), apart from screening for coeliac disease, which is 10 to 20 times more frequent in patients with D-IgA. In the case of a child with D-IgA with recurrent infections (mainly affecting the respiratory and, less commonly, the gastrointestinal tract), signs and symptoms of alarm must always be sought and valued for other types of primary immunodeficiency (especially the common variable immunodeficiency), which, although rarely, can be associated with D-IgA. Patients with D-IgA, in particular adolescents and adults, have a higher risk than the general population of developing autoimmune diseases. The family should be informed of this possible occurrence, but specific laboratory evaluations are not necessary. Four clinical cases are presented: an occasional finding of D-IgA in a healthy child, the association with coeliac disease, the association with juvenile idiopathic arthritis, and IgA deficiency in a patient with an immunodeficiency disorder (ataxia-telangectasia).

Precision medicine in clinical oncology: the journey from IgG antibody to IgE.

Cancer is one of the leading causes of death and the incidence rates are constantly rising. The heterogeneity of tumors poses a big challenge for the treatment of the disease and natural antibodies additionally affect disease progression. The introduction of engineered mAbs for anticancer immunotherapies has substantially improved progression-free and overall survival of cancer patients, but little efforts have been made to exploit other antibody isotypes than IgG. In order to improve these therapies, 'next-generation antibodies' were engineered to enhance a specific feature of classical antibodies and form a group of highly effective and precise therapy compounds. Advanced antibody approaches include among others antibody-drug conjugates, glyco-engineered and Fc-engineered antibodies, antibody fragments, radioimmunotherapy compounds, bispecific antibodies and alternative (non-IgG) immunoglobulin classes, especially IgE. The current review describes solutions for the needs of next-generation antibody therapies through different approaches. Careful selection of the best-suited engineering methodology is a key factor in developing personalized, more specific and more efficient mAbs against cancer to improve the outcomes of cancer patients. We highlight here the large evidence of IgE exploiting a highly cytotoxic effector arm as potential next-generation anticancer immunotherapy.

Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences.

The integrity of the genome is under constant threat of environmental and endogenous agents that cause DNA damage. Endogenous damage is particularly pervasive, occurring at an estimated rate of 10,000–30,000 per cell/per day, and mostly involves chemical DNA base lesions caused by oxidation, depurination, alkylation, and deamination. The base excision repair (BER) pathway is primary responsible for removing and repairing these small base lesions that would otherwise lead to mutations or DNA breaks during replication. Next to preventing DNA mutations and damage, the BER pathway is also involved in mutagenic processes in B cells during immunoglobulin (Ig) class switch recombination (CSR) and somatic hypermutation (SHM), which are instigated by uracil (U) lesions derived from activation-induced cytidine deaminase (AID) activity. BER is required for the processing of AID-induced lesions into DNA double strand breaks (DSB) that are required for CSR, and is of pivotal importance for determining the mutagenic outcome of uracil lesions during SHM. Although uracils are generally efficiently repaired by error-free BER, this process is surprisingly error-prone at the Ig loci in proliferating B cells. Breakdown of this high-fidelity process outside of the Ig loci has been linked to mutations observed in B-cell tumors and DNA breaks and chromosomal translocations in activated B cells. Next to its role in preventing cancer, BER has also been implicated in immune tolerance. Several defects in BER components have been associated with autoimmune diseases, and animal models have shown that BER defects can cause autoimmunity in a B-cell intrinsic and extrinsic fashion. In this review we discuss the contribution of BER to genomic integrity in the context of immune receptor diversification, cancer and autoimmune diseases.

Impact of immunoparesis on clinical outcomes following bone marrow transplantation.

e20505 Background: Immunoparesis (hypogammaglobinemia) has been shown to impact outcomes in patients with newly diagnosed multiple myeloma (MM). Its impact in the post-transplant setting and potential risk of both infections and immune dysregulation impacting relapse is less clear. We sought to assess the role of immunoparesis both pre and post autologous stem cell transplant (ASCT) in newly diagnosed MM patients. Our primary outcome was the impact of immunoparesis on progression free survival (PFS) post-ASCT controlling for maintenance therapy. Methods: We evaluated all MM patients between 2008 and 2017 at Loyola University who underwent ASCT. Inclusion criteria included first ASCT and age > 18 years. We evaluated both the presence of and number of impacted immunoglobulin (Ig) classes pre-transplant and day 100, 6-months, and 12 months post-ASCT. Results: The most common MM isotype was IgG Kappa (41.01%). Immunoparesis pre-ASCT and post-ASCT at day 100, 6 months, and 12 months was seen in 75%, 89.5%, 80%, and 58.5% respectively. Median time from diagnosis to transplant was 7.75 months (5.98 – 13.73). When adjusting for pre-transplant response, conditioning regimen, and post-transplant maintenance, neither the absolute presence of or number of Ig-classes impacting was predictive of hazard of disease progression or death (OS) while ISS-stage, best response post ASCT, and time from diagnosis to transplant were (table). Conclusions: Contrary to studies in the pre-transplant setting, our analysis indicates that immunoparesis is not predictive of relapse or survival in the post-transplant setting, suggesting modification of disease process with treatment and ASCT. When controlled for maintenance therapy, immunoparesis does not increase risk of progression or decrease overall survival alleviating the concern for increased morbidity/mortality secondary to infections in the face of immunoparesis in the era of maintenance therapy. [Table: see text]

Influence of cadmium on the cellular part of the immune system of young cattle

The article presents the results of research on the effect of cadmium load on the body of young cattle. The negative effect of Cadmium on the liver causes a wide range of pathological changes at different levels of its organization. The impact of heavy metals on the immune system is particularly significant, because it performs a leading role in maintaining health and is recognized as one of the most sensitive to adverse factors, even in relatively low concentrations. The aim of the study was to investigate the influence of cadmium on the cellular part of the immune system of young cattle. The research was carried out on 10 bulls of six months of age, Ukrainian black-and-white dairy breed, which were formed into 2 groups of 5 animals each: control and experimental. The bulls of the control group were on a normal diet. Animals of the experimental group were administered cadmium chloride at a dose of 0.04 mg/kg body weight of the animal. It was found that feeding bulls with a diet of cadmium chloride, the number of B-lymphocytes on the 5th day of the experiment was 17.54 ± 0.95 %. The lowest number of B-lymphocytes was on the 20th day of testing – 15.12 ± 0.37 %. The study of the number of T-lymphocytes shows that at the beginning of analysis the number of T-lymphocytes in the blood of animals of the control and experimental groups ranged from 40.70 ± 3.62 and 40.85 ± 2.54 %. Subsequently, the number of T-lymphocytes in the blood of the experimental group began to decline. The lowest number of T-lymphocytes was in the experimental group of animals on the 20th day of the research, compared with the control group, this figure decreased by 3.63 %. The state of immunity of animals under cadmium load significantly depends on the ratio of T-helpers to T-suppressors. It was found that the immunoregulatory index of blood of bulls of the experimental group probably decreased from 10 days of the research. The number of T-helper lymphocytes in the blood of the experimental group of bulls under cadmium loading is probably reduced by 15, 20 and 30 days of testing. A probable increase in the number of T-suppressors was noted in the bull's blood of the experimental group on the 20th day of the research. Immunoglobulins of different classes are crucial among bull’s serum proteins under cadmium loading. The concentration of immunoglobulins in the blood under cadmium load decreased by 15.9 % relative to the control group on the 20th day of analysis.

Immunoglobulins on the surface of differently charged polymer nanoparticles.

The overall success of nanocarriers in biomedical applications depends on their interaction with different proteins in blood. Immunoglobulins as a major protein class of the blood proteome may considerably influence the identity of the nanocarriers in blood. However, there is a lack of knowledge about the specific details of the interaction mechanism between different immunoglobulins and nanocarriers. Therefore, the authors have investigated the interaction of different immunoglobulin classes-namely, immunoglobulin G, A, and M-with different polystyrene model nanoparticles. The authors report that immunoglobulin interaction with nanoparticles strongly depends on the immunoglobulin class and surface charge of the nanoparticles. Furthermore, upon adsorption on the nanoparticles' surfaces, aggregation processes and denaturation of immunoglobulins were observed. This highlights the importance of nanocarriers' design in order to prevent unfavorable denaturation and adsorption processes of immunoglobulins on nanoparticle surfaces.

The role of ERK2 in regulating germinal center B cell fate decisions

Abstract The regulation of B cell activation, differentiation, and survival is a crucial control point for the maintenance of B cell tolerance in the germinal center (GC) and involves the precise coordination of several complex intracellular signaling pathways. Dysregulation of these pathways can lead to the generation and persistence of autoreactive memory B cells and antibody-secreting cells (ASCs), resulting in autoimmune disease. The mitogen-activated protein kinase (MAPK) pathway is central to signals required for GC B cell selection and differentiation, such as those received through the B cell receptor (BCR) and C-X-C chemokine receptor type 4 (CXCR4), respectively. Extracellular signal-regulated kinases 1 and 2 (ERK1/2), important effectors of this pathway, play a major role in B cell activation and differentiation. Though ERK2 specifically regulates the pro-apoptotic protein, Bmf, its role in regulating GC B cell fate is unknown. Our lab has developed a mouse model in which the deletion of Erk2 is accompanied by the expression of the fluorescent reporter protein, eYFP, allowing us to identify and isolate viable Erk2Δ B cells using flow cytometry. Preliminary data using this model has shown that peripheral Erk2Δ B cells express DEC205, which is associated with follicular T helper cell interactions and CD80, which is involved in co-stimulation and immunoglobulin class switching. Thus, we hypothesize that ERK2 regulates several aspects of GC B cell selection. Our results will help elucidate the molecular mechanisms underlying B cell differentiation, potentially offering new approaches to treating B cell-driven autoimmune diseases.

Particular paraclinical indices in newborn sepsis patients whose parents constantly lived in different environmental conditions

Xenobiotics can have a variety of effects on the human body, and especially on the course of intrauterine development. Numerous researchers point out that it is the nature of the environment that can negatively affect the course of certain diseases in both children and adults. Neonatal sepsis is one of the most serious diseases in neonatology practice. And, in our opinion, the topic of the influence of adverse environmental factors on the features of sepsis in newborns depending on the ecological situation of their parents' habitats is unclarified.The research aims at the particular paraclinical indices in children with neonatal sepsis whose parents constantly lived in different environmental conditions.Material and methods. To study the aim, a comprehensive survey of 260 newborns who suffered from neonatal sepsis in 2016-2018 was conducted. The groups have been formed based on the complex evaluation of the prolonged influence of the anthropogenic pollution of air, water and soil on the body of parents of newborns in the parts of the region. The ecological risk coefficient (ERC) has been proposed concerning the environmental situation in the regional centers. Thus, the first clinical group (the main group) included neonatal sepsis patients whose parents permanently lived in parts with an ERC of 2.0 or more and with unfavorable environmental characteristics of the regional center. The second group (comparison) was formed by newborns with sepsis, whose parents permanently lived in areas with a low risk of adverse effects of these environmental factors on their body (ERC<2.0).Results and discussion. The content of interleukins-6, -8.-10, C-reactive protein, presepsin and procalcitonin in the blood serum of patients with neonatal sepsis showed the activity of the systemic inflammatory response of the body to an infectious agent. It should be noted that high serum levels of interleukin-10, which has an anti-inflammatory effect, was more often registered in patients of the I clinical group. Thus, the blood content of this interleukin 35.0 pg/ml occurred in the newborn of the main group in 23.7% of cases, and in children of the comparison group – in 18.1% of observations. Along with a clearer identification of high levels of anti-inflammatory interleukin-10 inpatients of the I group, a significant decrease in serum concentrations of immunoglobulins of classes A, G, M was observed in these newborns.Conclusions. The decrease in the level of the above serum immunoglobulins is probably due to the immunosuppressive effect of xenobiotics on the fetus, whose mother was under the conditions of long-term action of xenobiotics. This, in turn, reduces the resistance of the newborn body to infection and contributes to a more severe course of the infectious process. Probably, the more severe manifestations of neonatal sepsis in newborns of the I clinical group are partly due to a combination of decreased immunoglobulin synthesis and increased interleukin-10 production.

Pharmacological assessment of immunotropic activity of new gel metabiotic on cellular and humoral immunity in experimentally modeled thermal skin burns

Thermal skin burns were experimentally modeled in laboratory animals revealed immunotropic effects of new gel metabiotic consisting of complex biological active substances produced by Bacillus subtilis B-3679 strain as part of three gel transcutaneous bases: tizol, eftiderm and organosilicon glycerohydrogel on cellular and humoral immunity. The aim of the study was to evaluate immunotropic activity of a new gel metabiotic on cellular and humoral immunity in experimentally modeled thermal skin burns in 60 white laboratory Wistar rats, weighed 180-220 g, for metabiotic consisting of a complex biologically active substances produced by Bacillus subtilis B-3679 strain containng the three gel transcutaneous bases: tizol, ephtiderm and organosilicon glycerohydrogel (KTGG). Registered, standardized antimicrobial and wound-healing ointment levosin was used as a control. The experimental data obtained confirm the effectiveness of using the drugs studied for treatment of first and second degree thermal burns revealed by faster decreased area of affected area compared to experimental animals treated with levosin. While evaluating therapeutic effectiveness of experimental samples of metabiotic-based gel preparations, their influence on various parameters of cellular and humoral immunity in modeled thermal skin burn was examined. We assessed phagocytic activity of blood neutrophils and peritoneal macrophages, quantified T and B lymphocytes, as well as antibody-forming cells and immunoglobulins of various classes. It was found that in experimental animals reproducing models of traumatic skin injuries, there is an increase in the level of all the studied parameters of humoral immunity. Concentration of immunoglobulin M, circulating immune complexes and immunoglobulin E, as well as various cytokines, increased larger. The level of α-interferon and the receptor antagonist interleukin-1 was elevated. Thus, the study of the humoral status of experimental animals that received test metabiotic-based gel preparations in modeled thermal skin burns, allows to conclude that they significantly influenced various arms both cellular and humoral immunity. More marked effects were observed for metabiotic-based drugs containing tizol and KTGG. In general, based on the experimental data we can conclude that the relatively high therapeutic effectiveness of examined drugs in the treatment of thermal skin burn wounds in experimental animals, use of which provided earlier removal of necrotic masses, accelerated regeneration processes, and prevented development of secondary wound infection in burns.

Frequency and specificity of alloantibodies to HNA system antigens in donors of blood and blood components

Aim. To study the rate of human neutrophil antigens (HNA) alloimmunization in donors of blood and blood components.
 Methods. The study included blood samples of 1,127 donors who donated blood and its components in the Russian Scientific and Research Institute of Hematology and Transfusiology, Saint Petersburg, 635 male and 492 female. 36.18% of female donors were aged between 18 and 30 (n=178) and 63.82% were aged between 30 and 60 (n=314). The medical histories of all donors did not contain the records about the transfusion of blood components. Screening and identification of HNA alloantibodies were performed using the flow cytometric granulocyte immunofluorescence test with monoclonal antibodies CD16-PE, CD45-PC7, CD19-APC, Goat F(ab')2 Anti-Human IgG-FITC and the panel of donor neutrophils with detected HNA genotypes.
 Results. The frequency of HNA alloantibodies in blood donors was 0.35% (n=4). No HNA alloantibodies were found in the male donors. Alloantibodies were detected only in female blood donors aged between 30 and 60. HNA antibody frequency in female donors was 0.81%. It were detected anti-HNA-1a, anti-HNA-3b and anti-HNA-4b antibodies of the IgG immunoglobulin class. In one donor, the specificity of antibodies could not be established. To establish whether detected antibodies in immunized donors were alloantibodies, HNA genotypes were determined.
 Сonclusion. HNA alloantibodies occur with low frequency and are determined in 0.35% of blood donors. Alloantibodies were detected only in female donors and were directed against HNA-1a, HNA-3b and HNA-4b. The frequency of HNA antibodies in female donors was 0.81%. HNA genotyping confirmed that detected antibodies were alloantibodies.

Immunodiagnostics, immunotherapy and immunoprophylaxis in the department of otolaryngology. Message 1. Optimal indicators of systemic immunity in assessing the clinical and laboratory status of patients with inflammatory diseases of the upper respiratory tract (analytical generalization)

Introduction: It is considered proven that the state of the immune system determines the development and course of many pathological processes, which are based on inflammation. At the same time, taking into account current trends in assessing the immunological status, conditional variants of deviation from the norm, a decrease in the number of cells from the average statistical norm of the region and control parameters in the performing laboratory by 1.5 or 2 times were adopted, since deviations are within 30-60 % are borderline and quite easily compensated by the body. The aim of the work was to conduct an integrated analysis of data to determine the state of systemic immunity in inflammatory diseases of the upper respiratory tract (URT) to select the optimal informa-tional indicators. Materials and methods: Immunological methods were used to examine 260 people with inflammatory pa-thology of the upper respiratory tract, of which 82 had chronic tonsillitis, 76 with chronic rhinitis, 70 with chronic pharyngitis and 32 people made up a control group of healthy donors. The age of the subjects ranged from 16 to 60 years, the duration of the disease from 1 year to 5 years, female patients predominated (≈60%). Examinations were conducted in the clinical remission stage. When assessing systemic immunity, the number of T-lymphocytes (CD 3, 4, 8), B-lymphocytes (CD22), NK (CD56), monocytes (CD14), concentration of immunoglobulins of classes M, G, A, E, cytokines with regulatory properties, interferon-γ-IL4 were determined. Functional tests in assessing systemic immunity are presented by determining the cytolytic activity of blood mononuclear cells in relation to avian xenogenic red blood cells and the activity of phagocytic blood cells in relation to latex particles at the absorption stage. Statistical processing was performed using the angular transfor-mation method "φ" according to Fisher and the "one-sided" criterion "U" Wilcoxon. Results: Based on a wide range of immunological studies in patients with chronic diseases of the upper respiratory tract, it seems most appropriate to use the following laboratory tests to assess systemic immunity to determine the characteristic deviations in the immune status of patients: High diagnostic value: - decreased serum IgA concentration (<0.5 g/l); - low level of activity of ECC of blood (<20% for xenoerythrocytes); - increased level of interleukin-1β (> 25 pg/ml); Relative diagnostic value: - determination of the degree of dysimmunoglobulinemia in serum; - increased titers of antibodies to streptolysin-O, other microbial antigens; - increased serum IgM. Conclusion: The developed criteria and approaches in assessing systemic immunity in patients with in-flammatory diseases of the upper respiratory tract can be used to examine patients and assess the effectiveness of the treatment.

Immune-Complexome Analysis Identifies Immunoglobulin-Bound Biomarkers That Predict the Response to Chemotherapy of Pancreatic Cancer Patients.

Pancreatic Ductal Adenocarcinoma (PDA) is an aggressive malignancy with a very poor outcome. Although chemotherapy (CT) treatment has poor efficacy, it can enhance tumor immunogenicity. Tumor-Associated Antigens (TAA) are self-proteins that are overexpressed in tumors that may induce antibody production and can be PDA theranostic targets. However, the prognostic value of TAA-antibody association as Circulating Immune Complexes (CIC) has not yet been elucidated, mainly due to the lack of techniques that lead to their identification. In this study, we show a novel method to separate IgG, IgM, and IgA CIC from sera to use them as prognostic biomarkers of CT response. The PDA Immune-Complexome (IC) was identified using a LTQ-Orbitrap mass spectrometer followed by computational analysis. The analysis of the IC of 37 PDA patients before and after CT revealed differential associated antigens (DAA) for each immunoglobulin class. Our method identified different PDA-specific CIC in patients that were associated with poor prognosis patients. Finally, CIC levels were significantly modified by CT suggesting that they can be used as effective prognostic biomarkers to follow CT response in PDA patients.

YY1 control of mitochondrial-related genes does not account for regulation of immunoglobulin class switch recombination in mice.

Immunoglobulin class switch recombination (CSR) occurs in activated B cells with increased mitochondrial mass and membrane potential. Transcription factor Yin Yang 1 (YY1) is critical for CSR and for formation of the DNA loops involved in this process. We therefore sought to determine if YY1 knockout impacts mitochondrial gene expression and mitochondrial function in murine splenic B cells, providing a potential mechanism for regulating CSR. We identified numerous genes in splenic B cells differentially regulated when cells are induced to undergo CSR. YY1 conditional knockout caused differential expression of 1129 genes, with 59 being mitochondrial-related genes. ChIP-seq analyses showed YY1 was directly bound to nearly half of these mitochondrial-related genes. Surprisingly, at the time when YY1 knockout dramatically reduces DNA loop formation and CSR, mitochondrial mass and membrane potential were not significantly impacted, nor was there a significant change in mitochondrial oxygen consumption, extracellular acidification rate, or mitochondrial complex I or IV activities. Our results indicate that YY1 regulates numerous mitochondrial-related genes in splenic B cells, but this does not account for the impact of YY1 on CSR or long-distance DNA loop formation.