<abstract>
<title style='display:none'>Abstract</title>
Elevated immunoglobulin G4 (IgG4) serum antibodies are an important feature of IgG4-related disease. However, IgG4 antibodies can play a role in autoimmune thyroid disorders. In this study, we aimed to evaluate the impact of serum IgG4 levels on clinical features of Graves’ disease (GD). We recruited 60 patients with GD (48 patients without thyroid eye disease, 12 patients with moderate-to-severe Graves’ orbitopathy [GO], and 25 healthy control subjects). The prevalence of high IgG4 serum concentration was 4.2% among GD patients without GO and 33.33% in patients with moderate-to-severe GO. The group with GO had significantly higher median IgG4 levels (87.9 mg/dL) than the control group (41.2 mg/dL, <italic>P</italic> = 0.034) and the GD without GO group (30.75 mg/dL, <italic>P</italic> &lt; 0.001). Patients with thyroid nodules had lower IgG4 levels than patients without thyroid nodules, but the difference was not statistically significant (35.7 [24.8; 41.53] mg/dL vs. 43 [30.1; 92.7] mg/dL, <italic>P</italic> = 0.064). IgG4 as a diagnostic tool for moderate-to-severe GO had the following parameters: area under the curve (AUC): 0.851 (<italic>P</italic> &lt; 0.001), at the cut-off value of 49 mg/dL, negative predictive value: 100%, positive predictive value: 48%, sensitivity: 100%, specificity: 73%. There were no significant differences between the high and normal IgG4 groups in thyroid hormones, antithyroid antibodies, and ultrasound features. Serum IgG4 levels are associated with some of the clinical features of GD and can help in the diagnostic process of the disease. More research is needed to better understand the pathophysiology of IgG4 involvement in GD.
</abstract>

Clinical Significance of IgG4 Serum Concentration in Graves’ Disease

<abstract>
<title style='display:none'>Abstract</title>
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of sensitive cancer cells, including colorectal cancer (CRC). Due to its short biological half-life after intravenous administration and related clinical ineffectiveness, novel formulations of TRAIL need to be developed. Here we propose <italic>Lactococcus lactis</italic> bacteria as a vehicle for local delivery of human soluble TRAIL (hsTRAIL) in CRC. The use of common probiotics targeting guts as carriers for TRAIL could ensure its sustained release at the tumor site and extend the duration of its activity. We have already engineered hsTRAIL-secreting <italic>L.lactis</italic> bacteria and showed their effectiveness in elimination of human CRC cells in vitro and in vivo in a mouse subcutaneous model. Here, <italic>L.lactis</italic>(hsTRAIL+) were administered by gastric gavage to SCID mice with orthotopically developed HCT116 tumor in cecum, in monotherapy or in combination with metformin (MetF), already shown to enhance the hsTRAIL anti-tumor activity in subcutaneous CRC model. Oral administration of <italic>L.lactis</italic>(hsTRAIL+) resulted in significant progression of HCT116 tumors and shortening of the colon crypts. Secretion of hsTRAIL in the colon was accompanied by infiltration of the primary tumor with M2-macrophages, while MetF promoted transient colonization of the gut by <italic>L.lactis</italic>. Our study indicates that <italic>L.lactis</italic> bacteria after oral administration enable delivery of biologically active hsTRAIL to colon, however its potential therapeutic effect in CRC treatment is abolished by its pro-tumorigenic signalling, leading to the recruitment of M2-macrophages and tumor growth promotion.
</abstract>

Human Soluble TRAIL Secreted by Modified <italic>Lactococcus lactis</italic> Bacteria Promotes Tumor Growth in the Orthotopic Mouse Model of Colorectal Cancer

<abstract>
<title style='display:none'>Abstract</title>
Pregnancy is a remarkable event where the semi-allogeneic fetus develops in the mother’s uterus, despite genetic and immunological differences. The antigen handling and processing at the maternal–fetal interface during pregnancy appear to be crucial for the adaptation of the maternal immune system and for tolerance to the developing fetus and placenta. Maternal antigen-presenting cells (APCs), such as macrophages (Mφs) and dendritic cells (DCs), are present at the maternal–fetal interface throughout pregnancy and are believed to play a crucial role in this process. Despite numerous studies focusing on the significance of Mφs, there is limited knowledge regarding the contribution of DCs in fetomaternal tolerance during pregnancy, making it a relatively new and growing field of research. This review focuses on how the behavior of DCs at the maternal–fetal interface adapts to pregnancy’s unique demands. Moreover, it discusses how DCs interact with other cells in the decidual leukocyte network to regulate uterine and placental homeostasis and the local maternal immune responses to the fetus. The review particularly examines the different cell lineages of DCs with specific surface markers, which have not been critically reviewed in previous publications. Additionally, it emphasizes the impact that even minor disruptions in DC functions can have on pregnancy-related complications and proposes further research into the potential therapeutic benefits of targeting DCs to manage these complications.
</abstract>

Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy

<abstract>
<title style='display:none'>Abstract</title>
Venous thromboembolism, encompassing acute pulmonary embolism (APE) and deep vein thrombosis (DVT), is a potentially fatal disease with complex pathophysiology. Traditionally, the Virchow triad provided a framework for understanding the pathogenic contributors to thrombus formation, which include endothelial dysfunction, alterations in blood flow and blood hypercoagulability. In the last years, it has become apparent that immunity plays a central role in thrombosis, interacting with classical prothrombotic mechanisms, oxidative stress and vascular factors. Thrombosis amplifies inflammation, and exaggerated inflammatory processes can trigger thrombosis mainly due to the activation of leukocytes, platelets, and endothelial cells. APE-related endothelium injury is a major trigger for immune system activation. Endothelium is also a key component mediating inflammatory reaction and it is relevant to maintain vascular permeability. Exaggerated right ventricular wall stress and overload, with coexisting systemic hypotension and hypoxemia, result in myocardial injury and necrosis. Hypoxia, tissue factor activation and cytokine storm are engaged in the thrombo-inflammatory processes. Thrombus development is characterized by inflammatory state vascular wall caused mainly by an early extravasation of leukocytes and intense selectins and cytokines production. Nevertheless, immunity of DVT is well described, little is known about potential chemokine and cellular differences between thrombus that develops in the vein and thrombus that detaches and lodges in the pulmonary circulation being a cause of APE. There is a paucity of data considering inflammatory state in the pulmonary artery wall during an acute episode of pulmonary embolism. The main aim of this review is to summarize the knowledge of immunity in acute phase of pulmonary embolism in experimental models.
</abstract>

Acute Pulmonary Embolism and Immunity in Animal Models

<abstract>
<title style='display:none'>Abstract</title>
Most gastric cancers (GC) are thought to be caused by <italic>Helicobacter pylori</italic> (<italic>H. pylori</italic>) infections. However, there is mounting evidence that GC patients with positive <italic>H. pylori</italic> status have improved prognoses. The <italic>H. pylori</italic>-induced cellular immune reaction may inhibit cancer. In this study, BALB/c mice were immunized using recombinant plasmids that encode the <italic>ureF</italic> gene of <italic>H. pylori</italic>. Purified functional splenic CD3+ T lymphocytes are used to study the anticancer effects <italic>in vitro</italic> and <italic>in vivo</italic>. The immunological state of GC patients with ongoing <italic>H. pylori</italic> infection is mimicked by the <italic>H. pylori</italic> DNA vaccines, which cause a change in the reaction from Th1 to Th2. Human GC cells grow more slowly when stimulated CD3+ T lymphocytes are used as adoptive infusions because they reduce GC xenograft development <italic>in vivo</italic>. The more excellent ratios of infiltrating CD8+/CD4+ T cells, the decreased invasion of regulatory FOXP3+ Treg lymphocytes, and the increased apoptosis brought on by Caspase9/Caspase-3 overexpression and Survivin downregulation may all contribute to the consequences. Our findings suggest that in people with advanced GC, <italic>H. pylori</italic> pIRES2-DsRed-Express-<italic>ureF</italic> DNA vaccines may have immunotherapeutic utility.
</abstract>

Potential Gastric Cancer Immunotherapy: Stimulating the Immune System with <italic>Helicobacter pylori</italic> pIRES2-DsRed-Express-<italic>ureF</italic> DNA Vaccines

<abstract>
<title style='display:none'>Abstract</title>
The immune system is regulated by a complex set of genetic, molecular, and cellular interactions. Rapid advances in the study of immunity and its network of interactions have been boosted by a spectrum of “omics” technologies that have generated huge amounts of data that have reached the status of big data (BD). With recent developments in artificial intelligence (AI), theoretical and clinical breakthroughs could emerge. Analyses of large data sets with AI tools will allow the formulation of new testable hypotheses open new research avenues and provide innovative strategies for regulating immunity and treating immunological diseases. This includes diagnosis and identification of rare diseases, prevention and treatment of autoimmune diseases, allergic disorders, infectious diseases, metabolomic disorders, cancer, and organ transplantation. However, ethical and regulatory challenges remain as to how these studies will be used to advance our understanding of basic immunology and how immunity might be regulated in health and disease. This will be particularly important for entities in which the complexity of interactions occurring at the same time and multiple cellular pathways have eluded conventional approaches to understanding and treatment. The analyses of BD by AI are likely to be complicated as both positive and negative outcomes of regulating immunity may have important ethical ramifications that need to be considered. We suggest there is an immediate need to develop guidelines as to how the analyses of immunological BD by AI tools should guide immune-based interventions to treat various diseases, prevent infections, and maintain health within an ethical framework.
</abstract>

Artificial Intelligence, Big Data, and Regulation of Immunity: Challenges and Opportunities

<abstract>
<title style='display:none'>Abstract</title>
Rheumatoid arthritis (RA) is a complex autoimmune disease that leads to joint destruction. A number of immune cells that affect joint tissues are involved in the pathogenesis of this disease. This leads to the synthesis of many pro-inflammatory mediators. The transport of drugs, as well as many cytokines involved in the development of inflammation in RA patients, is mediated by membrane transporters. Membrane transporters are proteins that mediate the transfer of substrates across biological membranes. But to date there are no studies examining the expression of solute carrier (SLC) transporters in joint tissues. The aim of the study was to evaluate the expression of individual SLC family transporters in the synovial membranes (SMs) and infrapatellar fat pad (Hoffa’s pad) of RA patients. The study included 20 patients with rheumatoid arthritis and 20 with osteoarthritis as the control group who were undergoing joint replacement surgery as a normal part of clinical care. In the SM and Hoffa’s pad of RA patients the following 17 membrane transporters were defined at relevant expression levels for SLC transporter superfamily: <italic>SLC15A2, SLC16A3, SLC19A1, SLC2A9, SLC22A1, SLC22A3, SLC22A4, SLC22A5, SLC22A18, SLC33A1, SLC47A1, SLC51A, SLC7A5, SLC7A6, SLC01C1, SLC02B1, SLC04A1</italic>. The confirmed expression of these transporters in the SMs as well as Hoffa’s pad of patients with RA and OA, and the differences in their expression between these groups, suggests the involvement of SLC transporters in both the maintenance of homeostasis under physiological conditions in the tissues of the joints, as well as in the inflammatory process in RA.
</abstract>

Solute Carrier Transporters in Synovial Membrane and Hoffa’s Pad of Patients with Rheumatoid Arthritis

<abstract>
<title style='display:none'>Abstract</title>
Foot-and-mouth disease virus (FMDV) is a highly contagious and economically devastating pathogen that affects cloven-hoofed animals worldwide. FMDV infection causes vesicular lesions in the mouth, feet, and mammary glands, as well as severe systemic symptoms such as fever, salivation, and lameness. The pathogenesis of FMDV infection involves complex interactions between the virus and the host immune system, which determine the outcome of the disease. FMDV has evolved several strategies to evade immune recognition and elimination, such as antigenic variation, receptor switching, immune suppression, and subversion of innate and adaptive responses. This review paper summarizes the current knowledge on the pathogenesis of FMDV infection and the mechanisms of immune evasion employed by the virus. It also discusses the challenges and opportunities for developing effective vaccines and therapeutics against this important animal disease.
</abstract>

The Pathogenesis of Foot-and-Mouth Disease Virus Infection: How the Virus Escapes from Immune Recognition and Elimination

<abstract>
<title style='display:none'>Abstract</title>
The aim of the present study was to determine the associations between the <italic>MICB</italic> genetic variability and the expression and the risk of development of post-transplant complications after allogeneic hematopoietic stem cell transplantation (HSCT). HSCT recipients and their donors were genotyped for two <italic>MICB</italic> polymorphisms (rs1065075, rs3828903). Moreover, the expression of a soluble form of MICB was determined in the recipients' serum samples after transplantation using the Luminex assay. Our results revealed a favorable role of the <italic>MICB</italic> rs1065075 <italic>G</italic> allele. Recipients with donors carrying this genetic variant were less prone to developing chronic graft-versus-host disease (cGvHD) when compared to recipients without any symptoms of this disease (41.41% <italic>vs.</italic> 65.38%, <italic>p</italic> = 0.046). Moreover, the <italic>MICB</italic> rs1065075 <italic>G</italic> allele was associated with a lower incidence of cytomegalovirus (CMV) reactivation, both as a donor (<italic>p</italic> = 0.015) and as a recipient allele (<italic>p</italic> = 0.039). The <italic>MICB</italic> rs1065075 <italic>G</italic> variant was also found to be associated with decreased serum soluble MICB (sMICB) levels, whereas serum sMICB levels were significantly higher in recipients diagnosed with CMV infection (<italic>p</italic> = 0.0386) and cGvHD (<italic>p</italic> = 0.0008) compared to recipients without those complications. A protective role of the <italic>G</italic> allele was also observed for the rs3828903 polymorphism, as it was more frequently detected among donors of recipients without cGvHD (89.90% <italic>vs.</italic> 69.23%; <italic>p</italic> = 0.013). <italic>MICB</italic> genetic variants, as well as serum levels of sMICB, may serve as prognostic factors for the risk of developing cGvHD and CMV infection after allogeneic HSCT.
</abstract>

MICB Genetic Variants and Its Protein Soluble Level Are Associated with the Risk of Chronic GvHD and CMV Infection after Allogeneic HSCT

<abstract>
<title style='display:none'>Abstract</title>
This is an animal model study to investigate changes in hemostasis during endotoxemic shock and to determine whether the combination of inhaled nitric oxide (iNO) + intravenous hydrocortisone had an effect on clot formation and fibrinolysis. iNO selectively decreases pulmonary artery pressure, without affecting cardiac index or systemic vascular resistance; however, the results of studies on the possible consequences of iNO administration on coagulation are inconsistent and require further research. Thirty-four piglets were included. Administering endotoxin caused severe hypodynamic shock. Half of the animals received iNO (30 ppm) + hydrocortisone, starting 3 h after endotoxin infusion and continuing to the end of the study. All animals developed coagulation disorders, manifested by a tendency to hypocoagulation; at the same time, fibrinolysis was impaired. Coagulation and fibrinolysis disorders persisted after endotoxin infusion was discontinued, with worse severity in the animals that died before the study was terminated. Administering iNO + hydrocortisone did not cause further changes in coagulation and fibrinolysis parameters, either during or after the endotoxin challenge, suggesting that potential therapeutic interventions with iNO to lower pulmonary arterial pressure will not affect hemostasis.
</abstract>

Abnormalities of Coagulation and Fibrinolysis Assessed by Thromboelastometry in an Endotoxic Shock Model in Piglets Treated with Nitric Oxide and Hydrocortisone

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Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is the peer-reviewed international journal, published only in electronic format since...

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Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is the peer-reviewed international journal,...

Archivum Immunologiae et Therapiae Experimentalis

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