Immunological Response Research Articles

New therapies for highly sensitized patients on the waiting list.

Exposure to HLA alloantigens through pregnancy, blood products and previous transplantations induce powerful immunologic responses that create an immunologic barrier to successful transplantation. This is commonly detected through screening for HLA antibodies using Luminex beads coated with HLA antigens at transplant evaluation. Currently accepted approaches to desensitization include plasmapheresis (PLEX)/low or high dose IVIg plus anti-CD20. However, these approaches are often unsuccessful due to the inability to remove high titer circulating HLA antibodies and limit rebound responses by long-lived anti-HLA antibody secreting plasma cells (PCs) and memory B-cells (BMEM). This is especially significant for patients with cPRA 99-100%. Newer desensitization approaches such as imlifidase (IgG endopeptidase) rapidly inactivates IgG molecules and creates an "antibody-free zone" by cleaving IgG into F(ab'2) and Fc fragments, thus eliminating complement and cell-mediated injury to the graft. This represents an important advancement in desensitization. However, the efficacy of imlifidase is limited by pathogenic antibody rebound, increasing the potential for antibody-mediated rejection. Controlling antibody rebound requires new strategies that address the issues of antibody depletion and inhibition of BMEM & PC responses. This will likely require a combination of agents that effectively and rapidly deplete pathogenic antibodies and prevent immune cell activation pathways responsible for antibody rebound. Here, using anti-IL-6R (tocilizumab) or anti-IL-6 (clazakizumab) could offer long-term control of BMEM and PC DSA responses. Agents aimed at eliminating long-lived PCs (anti-CD38 & anti-BCMAxCD3) are likely to benefit HS patients. Complement inhibitors and novel agents aimed at inhibiting Fc neonatal receptor (FcRn) IgG recycling will be important in desensitization. Administering these agents alone or in combination will advance our ability to effectively desensitize patients and maintain durable suppression post-transplant. After many years of limited options, advanced therapeutics will likely improve efficacy of desensitization and improve access to kidney transplantation for highly-HLA sensitized patients.

Phenotypic Landscape of Immune Cells in Sepsis: Insights from High-Dimensional Mass Cytometry.

Understanding the sepsis-induced immunological response can be facilitated by identifying phenotypic changes in immune cells at the single-cell level. Mass cytometry, a novel multiparametric single-cell analysis technique, offers considerable benefits in characterizing sepsis-induced phenotypic changes in peripheral blood mononuclear cells. Here, we analyzed peripheral blood mononuclear cells from 20 sepsis patients and 10 healthy donors using mass cytometry and employing 23 markers. Both manual gating and automated clustering approaches (PhenoGraph) were used for cell identification, complemented by uniform manifold approximation and projection (UMAP) for dimensionality reduction and visualization. Our study revealed that patients with sepsis exhibited a unique immune cell profile, marked by an increased presence of monocytes, B cells, and dendritic cells, alongside a reduction in natural killer (NK) cells and CD4/CD8 T cells. Notably, significant changes in the distributions of monocytes and B and CD4 T cells were observed. Clustering with PhenoGraph unveiled the subsets of each cell type and identified elevated CCR6 expression in sepsis patients' monocyte subset (PG#5), while further PhenoGraph clustering on manually gated T and B cells discovered sepsis-specific CD4 T cell subsets (CCR4low CD20low CD38low) and B cell subsets (HLA-DRlow CCR7low CCR6high), which could potentially serve as novel diagnostic markers for sepsis.

Diploid and triploid Chinook salmon (Oncorhynchus tshawytscha) exhibit differential immunological responses toacute thermal stress.

Exposure to temperatures outside of a fish's optimal range results in suppression of the immune system, ultimately leaving aquaculture stocks susceptible to disease outbreaks. This effect is exacerbated in triploid fishes, which demonstrate greater susceptibility to stress than their diploid counterparts. This study investigates the impacts of acute heat stress on the abundance of immune transcripts and proteins in diploid and triploid Chinook salmon (Oncorhynchus tshawytscha), an important finfish crop. This study also demonstrates that acute heat stress induces significant increases in the abundance hsp70, hsp90 and il1b transcripts in the head kidneys, gills and heart ventricles of both diploid and triploid Chinook salmon. Widespread dysregulation of antigen-presentation transcripts was also observed in fish of both ploidies. These results suggest that acute heat stress activates acute-phase responses in Chinook salmon and dysregulates antigen presentation, potentially leaving fish more susceptible to infection. At the protein level, IL-1β was differentially expressed in the head kidney and ventricles of diploid and triploid salmon following heat shock. Differential expression of two tapasin-like proteins in diploid and triploid salmon subjected to heat shock was also observed. Altogether, these data indicate that diploid and triploid Chinook salmon respond differently to acute thermal stressors.

Specific depletion of myeloid-derived suppressor cells by the chemotherapeutic agent 5-Fluorouracil enhances protective immune response in Paracoccidioidomycosis.

Paracoccidioidomycosis (PCM), a systemic mycosis in Latin America, is regulated by suppressive mechanisms mediated by tolerogenic plasmacytoid-dendritic-cells and regulatory T-cells. Our recent studies revealed that myeloid-derived suppressor cells (MDSCs), are important mediators in PCM. Their suppressive activity on Th1/Th17 immunity was shown to be mediated by inhibitory effect of IL-10, IDO-1 and PD-L1. Studies revealed the chemotherapeutic drug 5-Fluorouracil (5-FU) as a selective MDSC apoptosis-inducing agent, but its in vivo effect on infectious processes remains poorly investigated. MDSCs and other leukocytes were evaluated in the lungs of 5-FU-treated mice after four, six, and eight weeks of P. brasiliensis infection. Disease severity and immunological response were evaluated in MDSCs-depleted. 5-FU treatment caused a significant reduction of pulmonary MDSCs and fungal loads. The specific depletion of MDSCs by 5-FU reduced all pulmonary CD4+ T-cell populations (Th1, Th2, Th17, and Treg) resulting in improved tissue pathology and increased survival rates. Importantly, this reduction was concomitant with increased frequencies of Th1/Th17 cells and the increased levels of Th1/Th2/Th17 cytokines in the lungs and liver of treated mice suggesting an early and efficient protective effect of these cells. Furthermore, the immuneprotection conferred by the specific depletion of MDSCs by 5FU treatment could be reversed by the adoptive transfer of MDSCs. 5-FU treatment depletes lung-MDSCs of P. brasiliensis-infected mice resulting in enhanced immunity. The protective effect of 5-FU treatment in pulmonary PCM suggests that the specific depletion of MDSCs can be viewed as a potential immunotherapeutic tool for PCM.

Analysis of Comorbidity in HIV–Infected Patients with Immunological Inefficiency of Antiretroviral Therapy

Introduction. Studies indicate high risks of secondary diseases and adverse events not related to HIV in patients with immunological inefficiency of antiretroviral therapy (ART). The effect of comorbidity on the increase of CD4+ is detected.The aim of the study is assessing the effect of comorbidity on CD4+ growth and the probability of developing immunological inefficiency of ART.Materials and methods. A retrospective study was conducted that included HIV-infected patients with CD4+ at the beginning of treatment <200 cells/µl. Two groups were formed: the main group — patients with immunological inefficiency of ART (281 people); the control group — patients with sufficient immunological response on ART (188 people). Results. The probability of developing immunological inefficiency in patients with tuberculosis was 1.7 times higher (odds ratio (OR) — 1.7; 95 % confidence interval (CI) — 1.0–2.9); in patients with HCV-infection — 1.8 times higher (OR — 1.8; 95 % CI — 2.6–1.2). The probability of cardiovascular disease in the main group was 2 times higher (OR — 2.3; 95 % CI — 1.0–5.4).Discussion. Tuberculosis, HCV-infection and cardiovascular diseases frequently registered in the structure comorbidity in the main group of patients.Conclusion. According to the results of this study, HIV-infected patients with HCV and tuberculosis co-infection have a higher chance of developing immunological inefficiency of ART.

Influence of cryoablation versus operation on circulating lymphocyte subsets in patients with early-stage renal cell carcinoma

Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described.The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group.We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months.Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months.

Dietary Protease Supplementation Improved Growth Performance and Nutrients Digestion via Modulating Intestine Barrier, Immunological Response, and Microbiota Composition in Weaned Piglets

Despite mounting evidence for dietary protease benefits, the mechanisms beyond enhanced protein degradation are poorly understood. This study aims to thoroughly investigate the impact of protease addition on the growth performance, intestinal function, and microbial composition of weaned piglets. Ninety 28-day-old weaned pigs were randomly assigned to the following three experimental diets based on their initial body weight for a 28-day experiment: (1) control (CC), a basic diet with composite enzymes without protease; (2) negative control (NC), a diet with no enzymes; and (3) dietary protease (PR), a control diet with protease. The results show that dietary proteases significantly enhanced growth performance and boosted antioxidant capacity, increasing the total antioxidant capacity (T-AOC) levels (p < 0.05) while reducing malonaldehyde levels (p < 0.05). Additionally, protease addition reduced serum levels of inflammatory markers TNF-α, IL-1β, and IL-6 (p < 0.05), suppressed mRNA expression of pro-inflammatory factors in the jejunum (p < 0.01), and inhibited MAPK and NF-κB signaling pathways. Moreover, protease-supplemented diets improved intestinal morphology and barrier integrity, including zonula occludens protein 1(ZO-1), Occludin, and Claudin-1 (p < 0.05). Microbiota compositions were also significantly altered by protease addition with increased abundance of beneficial bacteria (Lachnospiraceae_AC2044_group and Prevotellaceae_UCG-001) (p < 0.05) and reduced harmful Terrisporobacter (p < 0.05). Further correlation analysis revealed a positive link between beneficial bacteria and growth performance and a negative association with inflammatory factors and intestinal permeability. In summary, dietary protease addition enhanced growth performance in weaned piglets, beneficial effects which were associated with improved intestinal barrier integrity, immunological response, and microbiota composition.

An open-label, phase IV randomised controlled trial of two schedules of a four-component meningococcal B vaccine in UK preterm infants

ObjectiveTo compare immunological responses of preterm infants to a four-component meningococcal B vaccine (4CMenB; Bexsero) following a 2+1 vs a 3+1 schedule, and to describe reactogenicity of routine vaccines.DesignAn open-label,...

Elucidating the role of prickly pear fruits (Opuntia littoralis) in mitigation of cadmium toxicity in Nile tilapia: impacts on haemato-biochemical and immunological responses

Elucidating the role of prickly pear fruits (Opuntia littoralis) in mitigation of cadmium toxicity in Nile tilapia: impacts on haemato-biochemical and immunological responses

A mathematical model for wound healing in the reef-building coral Pocillopora damicornis

Coral reefs, among the most diverse ecosystems on Earth, currently face major threats from pollution, unsustainable fishing practices , and perturbations in environmental parameters brought on by climate change. Corals also sustain regular wounding from other sea life and human activity. Recent reef restoration practices have even involved intentional wounding by systematically breaking coral fragments and relocating them to revitalize damaged reefs, a practice known as microfragmentation. Despite its importance, very little research has explored the inner mechanisms of wound healing in corals. Some reef-building corals have been observed to initiate an immunological response to wounding similar to that observed in mammalian species. Utilizing prior models of wound healing in mammalian species as the mathematical basis, we formulated a mechanistic model of wound healing, including observations of the immune response and tissue repair in scleractinian corals for the species Pocillopora damicornis. The model consists of four differential equations which track changes in remaining wound debris, number of cells involved in inflammation, number of cells involved in proliferation, and amount of wound closure through re-epithelialization. The model is fit to experimental wound size data from linear and circular shaped wounds on a live coral fragment. Mathematical methods, including numerical simulations and local sensitivity analysis, were used to analyze the resulting model. The parameter space was also explored to investigate drivers of other possible wound outcomes. This model serves as a first step in generating mathematical models for wound healing in corals that will not only aid in the understanding of wound healing as a whole, but also help optimize reef restoration practices and predict recovery behavior after major wounding events.

Potential Efficacy of Toxoplasma gondii Extracellular Vesicles in Protection against Acute Experimental Toxoplasmosis

Abstract Toxoplasmosis is a zoonotic disease thought to infect 1.5 billion people worldwide. It is a significant food- and water-borne illness that can lead to a major opportunistic infection in patients with impaired immune systems. As a result, there is a pressing need to provide better alternatives for effective long-term disease control, such as vaccinations, as there is no treatment that can eradicate bradyzoites within tissue cysts. Exosomes are multivesicular entities that fuses with plasma membranes to form nanograde membrane-bound vesicles that are secreted by the majority of cell types. Exosomes play important functions in intercellular communication and several of them are well described and known to have immunomodulatory capabilities. Exosomes generated from Toxoplasma gondii (T. gondii) were isolated and their protective effectiveness and immunological responses against acute T. gondii infection in mice was investigated. T. gondii exosomes were isolated and identified by transmission electron microscopy. Mice were immunized with T. gondii tachyzoites derived exosomes (100 μg, 3 doses intramuscular with 2 weeks interval) to investigate the vaccine’s efficiency by challenging the mice with T. gondii RH strain tachyzoites administered intraperitoneal. Exosomes from T. gondii were successfully isolated and characterized. T. gondii exosome-immunized mice showed a longer survival rate compared to the unimmunized group. T. gondii derived exosomes could be a promising vaccine candidate for protection against toxoplasmosis.

Analgesic Effect of Intrathecal Nalbuphine versus Intrathecal Fentanyl as Adjuvant to 0.5% Bupivacaine for Cesarian Section under Spinal Anaesthesia

Abstract Background One of the main objectives of anesthesia is to alleviate the patient’s pain and agony, by ensuring the performance of surgical procedures without any discomfort. Elimination of postoperative pain is indispensable due to the central, peripheral and immunological stress response to tissue injury. So there is a need for extended analgesia without any side effects to achieve this goal. The use of opioids in intrathecal or epidural anesthesia has become common to increase postoperative analgesia. However, opioid-induced side effects, such as respiratory depression, nausea, vomiting, urinary retention and pruritus, limit their use. Objective To assess the postoperative analgesic requirements and the spinally mediated analgesic effects of intrathecal nalbuphine as an adjuvant to intrathecal bupivacaine after cesarean section in comparison to intrathecal bupivacaine with fentanyl. Methods This randomized comparative clinical trial was conducted in Ain Shams University Hospitals’ operating rooms on 48 patients undergoing cesarean section within a period of six months after approval of ethical committee of Faculty of Medicine, Ain Shams University. Results This study showed that the addition of a small dose of nalbuphine or fentanyl to bupivacaine in spinal anesthesia prolonged the time of postoperative analgesia. In this study, there was no significant difference regarding the demographic data, duration of operation, maximum sensory level, and maximum motor blockade level. Adding to this, there was also no significant changes regarding the vital data of the patients. On the other hand, there was a significant difference regarding the duration of analgesia which was longer with nalbuphine. It was also noticed that with nalbuphine less patients required rescue analgesia in comparison to fentanyl. There was higher number of side effects recorded with fentanyl in comparison to nalbuphine. Conclusion Either intrathecal nalbuphine (0.8 mg) or intrathecal fentanyl (25 μg) combined with Bupivacaine improves intraoperative analgesia and prolongs post- operative analgesia in cesarean section. There was statistically significant difference between them, intrathecal nalbuphine had a prolonged duration of post-operative analgesia, lesser amount of rescue analgesia needed and fewer side effects than intrathecal fentanyl.

Comparative Study between Modified Pectoral Nerve Block versus Serratus Block for Analgesia For Modified Radical Mastectomy

Abstract Background One of the main objectives of anesthesia is to alleviate the patient’s pain and agony, by ensuring the performance of surgical procedures without any discomfort. Elimination of postoperative pain is indispensable due to the central, peripheral and immunological stress response to tissue injury. So there is a need for extended analgesia without any side effects to achieve this goal. Objective To assess the analgesic efficiency and safety of both Modified Pectoral Nerve Block versus Serratus Block in cases of modified radical mastectomy (MRM). The duration of analgesia and effect on hemodynamic parameters were evaluated. Moreover, undesirable side effects were studied. Patients and Methods The purpose of this study was to evaluate the effect of both PECS II block versus and Serratus anterior block in patients undergoing modified radical mastectomy surgery. The duration of analgesia and effect on hemodynamics parameters were evaluated. Moreover, undesirable side effects were studied. forty patients were randomly allocated into two equal groups (20 patients): group (A) and group (B). Group (A): received a PECSII block with 30 mL of bupivacaine 0.25%. Group(B): received a serratus anterior plane block (SAPB) using the same volume of 30 ml bupivacaine 0.25%. Results This study demonstrated that PECSII and serratus blocks have comparable analgesic properties in patients undergoing modified radical mastectomy. Both blocks were associated with reduced postoperative pain intensity and morphine consumption, intraoperative fentanyl requirement, and prolonged analgesia. The two blocks were associated with hemodynamic stability and absence of major complications characterizes both blocks. Conclusion This study confirms that PECSII and serratus blocks provide similarly adequate analgesia following modified radical mastectomy.

DNA structural features and variability of complete MHC locus sequences.

The major histocompatibility (MHC) locus, also known as the Human Leukocyte Antigen (HLA) genes, is located on the short arm of chromosome 6, and contains three regions (Class I, Class II and Class III). This 5Mbp locus is one of the most variable regions of the human genome, yet it also encodes a set of highly conserved and important proteins related to immunological response. Genetic variations in this region are responsible for more diseases than in the entire rest of the human genome. However, information on local structural features of the DNA is largely ignored. With recent advances in long-read sequencing technology, it is now becoming possible to sequence the entire 5Mbp MHC locus, producing complete diploid haplotypes of the whole region. Here, we describe structural maps based on the complete sequences from six different homozygous HLA cell lines. We find long-range structural variability in the different sequences for DNA stacking energy, position preference and curvature, variation in repeats, as well as more local changes in regions forming open chromatin structures, likely to influence gene expression levels. These structural maps can be useful in visualizing large scale structural variation across HLA types, in particular when this can be complemented with epigenetic signals.

Ectonucleotidase inhibitors: targeting signaling pathways for therapeutic advancement-an in-depth review.

Ectonucleotidase inhibitors are a family of pharmacological drugs that, by selectively targeting ectonucleotidases, are essential in altering purinergic signaling pathways. The hydrolysis of extracellular nucleotides and nucleosides is carried out by these enzymes, which include ectonucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (CD73). Ectonucleotidase inhibitors can prevent the conversion of ATP and ADP into adenosine by blocking these enzymes and reduce extracellular adenosine. These molecules are essential for purinergic signaling, which is associated with a variability of physiological and pathological processes. By modifying extracellular nucleotide metabolism and improving purinergic signaling regulation, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) inhibitors have the potential to improve cancer treatment, inflammatory management, and immune response modulation. Purinergic signaling is affected by CD73 inhibitors because they prevent AMP from being converted to adenosine. These inhibitors are useful in cancer therapy and immunotherapy because they may improve chemotherapy effectiveness and alter immune responses. Purinergic signaling is controlled by NTPDase inhibitors, which specifically target enzymes involved in extracellular nucleotide breakdown. These inhibitors show promise in reducing immunological responses, thrombosis, and inflammation, perhaps assisting in the treatment of cardiovascular and autoimmune illnesses. Alkaline phosphatase (ALP) inhibitors alter the function of enzymes involved in dephosphorylation reactions, which has an impact on a variety of biological processes. By altering the body's phosphate levels, these inhibitors may be used to treat diseases including hyperphosphatemia and certain bone problems. This article provides a guide for researchers and clinicians looking to leverage the remedial capability of ectonucleotidase inhibitors in a variety of illness scenarios by illuminating their processes, advantages, and difficulties.

A Comprehensive Review on the Electrocardiographic Manifestations of Cardiac Sarcoidosis: Patterns and Prognosis.

Cardiac sarcoidosis (CS) refers to cardiac involvement in sarcoidosis and is usually associated with worse outcomes. This comprehensive review aims to elucidate the electrocardiographic (ECG) signs and features associated with CS, as well as examine modern techniques and their importance in CS evaluation. The exact pathogenesis of CS is still unclear, but it stems from an abnormal immunological response triggered by environmental factors in individuals with genetic predisposition. CS presents with non-cardiac symptoms; however, conduction system abnormalities are common in patients with CS. The most common electrocardiographic (ECG) signs include atrioventricular blocks and ventricular tachyarrhythmia. Distinct patterns, such as fragmented QRS complexes, T-wave alternans, and bundle branch blocks, are critical indicators of myocardial involvement. The application of advanced ECG techniques such as signal-averaged ECG, Holter monitoring, wavelet-transformed ECG, microvolt T-wave alternans, and artificial intelligence-supported analysis holds promising outcomes for opportune detection and monitoring of CS. Timely utilisation of inexpensive and readily available ECG possesses the potential to allow early detection and intervention for CS. The integration of artificial intelligence models into ECG analysis is a promising approach for improving the ECG diagnostic accuracy and further risk stratification of patients with CS.

Core needle biopsy changes the expression of TGFβ1 and TGFβRII at protein level, and the distribution of CD4 and CD8 positive T cells in primary breast cancer

Core needle biopsy (CNB) has become a paradigm in preoperative breast cancer (BC) diagnosis. Although considered safe, it is an invasive procedure, which changes the tumor microenvironment. It facilitates a tumor supportive immune response, induces epithelial-mesenchymal transition (EMT), and enables the release of circulating tumor cells. The cytokine Transforming Growth Factor β (TGFβ) with its pleiotropic immunologic functions has an important role in this process. The aim of this study was to clarify the specific impact of CNB on the activity of the TGFβ pathway in early BC. We compared formalin fixed paraffin embedded samples from CNBs to the corresponding surgical resection specimens (SRSs) of 49 patients with BC. We found that the expression of TGFβ1 at protein level was significantly higher in both tumor epithelial and benign stromal cells in the SRSs (p=0.001), whereas the expression of TGFβRII in tumor cells was lower (p=0.001). The frequency of intra tumoral CD8 and CD4 positive T lymphocytes was lower in SRSs (p=0081 and p=0001, respectively), while in the peripheral stroma their prevalence was increased (p=0001 and p=0012, respectively). Our results show that CNB changes the hallmarks of the TGFβ path way in early BC. These CNB-induced changes in the tumor and in its microenvironment suggest that the procedure may change the immunological anti-tumor response of the host.

Immune markers of severe acute pancreatitis.

Acute pancreatitis is a common acute inflammatory disorder of the pancreas, and its incidence has been increasing worldwide. Approximately 10% of acute pancreatitis progresses to severe acute pancreatitis (SAP), which carries significant morbidity and mortality. Disordered immune response to pancreatic injury is regarded as a key event that mediates systemic injury in SAP. In this article, we review recent developments in immune biomarkers of SAP and future directions for research. Given the importance of the NLRP3-inflammasome pathway in mediating systemic inflammatory response syndrome and systemic injury, recent studies have investigated associations of SAP with systemic levels of activators of NLRP3, such as the damage associated molecular patterns (DAMPs) for the first time in human SAP. For example, circulating levels of histones, mitochondrial DNAs, and cell free DNAs have been associated with SAP. A panel of mechanistically relevant immune markers (e.g., panel of Angiopoeitin-2, hepatocyte growth factor, interleukin-8 (IL-8), resistin and sTNF-α R1) carried higher predictive accuracies than existing clinical scores and individual immune markers. Of the cytokines with established relevance to SAP pathogenesis, phase 2 trials of immunotherapies, including tumor necrosis factor (TNF)-alpha inhibition and stimulation of IL-10 production, are underway to determine if altering the immunologic response can reduce the severity of acute pancreatitis (AP). Circulating systemic levels of various DAMPs and a panel of immune markers that possibly reflect activities of different pathways that drive SAP appear promising as predictive biomarkers for SAP. But larger multicenter studies are needed for external validation. Studies investigating immune cellular pathways driving SAP using immunophenotyping techniques are scarce. Interdisciplinary efforts are also needed to bring some of the promising biomarkers to the bedside for validation and testing for clinical utility. Studies investigating the role of and characterization of altered gut-lymph and gut-microbiota in severe AP are needed.

Clinical and immunological response to sublingual allergen-specific immunotherapy: cumulative dose-response relationship

Clinical and immunological response to sublingual allergen-specific immunotherapy: cumulative dose-response relationship

Analysis of machine learning based integration to identify the crosslink between inflammation and immune response in non-alcoholic fatty liver disease through bioinformatic analysis

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) is a major form of chronic liver disease. This study aimed to scrutinize the diagnostic biomarkers of NAFLD and their correlation with the immune microenvironment through bioinformatic analysis. MethodsTo identify genes associated with nonalcoholic fatty liver disease (NAFLD), we obtained microarray datasets (GSE63067 and GSE89632) from the Gene Expression Omnibus (GEO) database. Machine learning techniques such as Support Vector Machine (SVM), Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) were used to identify key genes. We performed gene ontology analysis to identify the driver pathways of NAFLD. External datasets (merging GSE48452, GSE66676 and GSE135251) were used to validate the identified genes and confirm protein levels by Western blotting. The CIBERSORT algorithm and immune-related techniques, such as ssGSEA, were used to assess the level of infiltration of different immune cell types and their functions. Finally, Spearman's analysis confirmed the relationship between pivotal genes and immune cells. ResultsHub genes (BBOX1, FOSB, NR4A2, RAB26 and SOCS2) were identified as potential biomarkers. This study demonstrates that these hub genes are significantly dysregulated in NAFLD, suggesting that they may be useful as diagnostic indicators and possible targets for treatment. Also covered are their possible effects on inflammation, immune cell activation, and liver damage in NAFLD. A better understanding of the intricate relationship between metabolic inefficiency, immunological response, and liver pathology in NAFLD may be gained from this work, which can lead to the development of new diagnostic tools and clinical treatments. ConclusionThe current study identified BBOX1, FOSB, NR4A2, RAB26 and SOCS2 as important diagnostic biomarkers for NAFLD. The study highlights the important function of immune cell infiltration in developing NAFLD. Their findings provide valuable molecular biological insights into the development of NAFLD and may lead to novel therapeutic strategies for treating this disease.