-
Frontiers in Immunology 2022NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of...
NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumulating evidence implicates aberrant NET production and/or reduced NET clearance, along with alterations of molecules involved in NETosis pathway, in humans and animals with lupus. The extruded nuclear antigens released by NET are a source of autoantigens, which can contribute to the breakdown of self-tolerance in lupus. Excessive NET can also promote the production of pro-inflammatory cytokine interferon-α, elicit direct cytotoxic effect on various renal cells, and cause capillary necrosis and podocyte loss. Additionally, NET can induce endothelial-to-mesenchymal transdifferentiation, which can promote activated myofibroblasts leading to extracellular matrix production. Thus, aberrant NETosis can play diverse roles, including autoantibody production, inflammation, and tissue damage, at different stages of lupus pathogenesis. Evidence suggests that treatments currently used in lupus may reduce NETosis, suggesting a potential utility of targeting NETosis to treat lupus. In fact, several approaches are being experimented to therapeutically target pathways of NETosis. Future studies should precisely delineate distinct roles of NETosis at different stages of lupus pathogenesis in humans, which would offer a rational basis for NETosis-targeting treatments in the clinic.
Topics: Animals; Autoantigens; Cell Death; Extracellular Traps; Inflammation; Neutrophils
PubMed: 35686129
DOI: 10.3389/fimmu.2022.895216 -
Medicine Nov 2022High monocyte to lymphocyte ratio (MLR) values may be associated with the risk of active tuberculosis (TB) infection in adults, infants, and postpartum women with HIV... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High monocyte to lymphocyte ratio (MLR) values may be associated with the risk of active tuberculosis (TB) infection in adults, infants, and postpartum women with HIV infection. It may also serve as an indicator of the effectiveness of anti-TB treatment. Thus, the main aim of this study is to ascertain the accuracy of MLR for the diagnosis of TB and its role in monitoring the effectiveness of anti-TB therapy.
METHODS
This systematic review and meta-analysis followed the preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. All statistical analyses were performed using STATA 11 and Meta-DiSc software. The Quality assessment of Diagnostic Accuracy Studies tool was used to evaluate the methodological quality of the included studies. The area under the hierarchical summary receiver-operating characteristic hierarchical summary ROC curve [(HSROC) curve (AUC)] was also calculated as an indicator of diagnostic accuracy.
RESULTS
A total of 15 articles were included in this study. Accordingly, the result showed that elevated MLR is associated with increased risks of TB disease [odd ratio = 3.11 (95% CI: 1.40-6.93)]. The pooled sensitivity and specificity of MLR for identifying TB were 79.5% (95% CI: 68.5-87.3) and 80.2% (95% CI: 67.3-88.9), respectively. The AUC of HSROC was 0.88 (95% CI: 0.857-0.903), indicating the excellent diagnostic performance of MLR for TB. This study also showed that there is a significant reduction in the MLR value after anti-TB treatment in TB patients (standardized mean difference = 0.68; 95% CI: 0.007, 1.43).
CONCLUSIONS
Generally, MLR can be considered as a crucial biomarker to identify TB and monitor the effectiveness of anti-TB therapy.
Topics: Infant; Adult; Humans; Female; Monocytes; HIV Infections; Tuberculosis; Lymphocytes; Sensitivity and Specificity
PubMed: 36343023
DOI: 10.1097/MD.0000000000031539 -
World Journal of Gastroenterology Sep 2020Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging...
BACKGROUND
Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM
To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS
A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS
There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival ( = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival ( = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant ( = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION
NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
Topics: Albumins; Bilirubin; Carcinoma, Hepatocellular; Child; Humans; Liver Neoplasms; Lymphocytes; Neutrophils; Prognosis; Retrospective Studies
PubMed: 32952347
DOI: 10.3748/wjg.v26.i33.5022 -
Frontiers in Immunology 2021Congenital infection of the fetus trans-placental passage of pathogens can result in severe morbidity and mortality. Even without transmission to the fetus, infection...
BACKGROUND
Congenital infection of the fetus trans-placental passage of pathogens can result in severe morbidity and mortality. Even without transmission to the fetus, infection of the placenta itself is associated with pregnancy complications including pregnancy loss and preterm birth. Placental macrophages, also termed Hofbauer cells (HBCs), are fetal-origin macrophages residing in the placenta that are likely involved in responding to placental infection and protection of the developing fetus. As HBCs are the only immune cell present in the villous placenta, they represent one of the final opportunities for control of infection and prevention of passage to the developing fetus.
OBJECTIVE AND RATIONALE
The objective of this review was to provide a systematic overview of the literature regarding HBC responses during infection in pregnancy, including responses to viral, bacterial, and parasitic pathogens.
METHODS
PubMed and Scopus were searched on May 20th, 2021, with no limit on publication date, to identify all papers that have studied placental macrophages/Hofbauer cells in the context of infection. The following search strategy was utilized: (hofbauer* OR "hofbauer cells" OR "hofbauer cell" OR "placental macrophage" OR "placental macrophages") AND [infect* OR virus OR viral OR bacteri* OR parasite* OR pathogen* OR LPS OR "poly(i:c)" OR toxoplasm* OR microb* OR HIV)].
OUTCOMES
86 studies were identified for review. This included those that investigated HBCs in placentas from pregnancies complicated by maternal infection and studies investigating HBC responses to pathogens or Pathogen-Associated Molecular Patterns (PAMPs). HBCs can be infected by a variety of pathogens, and HBC hyperplasia was a common observation. HBCs respond to pathogen infection and PAMPs by altering their transcriptional, translational and secretion profiles. Co-culture investigations demonstrate that they can replicate and transmit pathogens to other cells. In other cases, they may eliminate the pathogen through a variety of mechanisms including phagocytosis, cytokine-mediated pathogen elimination, release of macrophage extracellular traps and HBC-antibody-mediated neutralization. HBC responses differ across gestation and may be influenced by pre-existing immunity. Clinical information, including gestational age at infection, gestational age of the samples, mode of sample collection and pregnancy outcome were missing for the majority of studies.
Topics: Female; Fetus; Humans; Infant, Newborn; Macrophages; Pathogen-Associated Molecular Pattern Molecules; Placenta; Pregnancy; Premature Birth
PubMed: 35250964
DOI: 10.3389/fimmu.2021.756035 -
Virologica Sinica Feb 2021Tyro3, Axl, and Mertk (TAM) receptors play multiple roles in a myriad of physiological and pathological processes, varying from promoting the phagocytic clearance of...
Tyro3, Axl, and Mertk (TAM) receptors play multiple roles in a myriad of physiological and pathological processes, varying from promoting the phagocytic clearance of apoptotic cells, sustaining the immune and inflammatory homeostasis, maintaining the blood-brain barrier (BBB) integrity and central nervous system (CNS) homeostasis, to mediating cancer malignancy and chemoresistance. Growth arrest-specific protein 6 (Gas6) and protein S (Pros1) are the two ligands that activate TAM receptors. Recently, TAM receptors have been reported to mediate cell entry and infection of multitudinous enveloped viruses in a manner called apoptotic mimicry. Moreover, TAM receptors are revitalized during viral entry and infection, which sequesters innate immune and inflammatory responses, facilitating viral replication and immune evasion. However, accumulating evidence have now proposed that TAM receptors are not required for the infection of these viruses in vivo. In addition, TAM receptors protect mice against the CNS infection of neuroinvasive viruses and relieve the brain lesions during encephalitis. These protective effects are achieved through maintaining BBB integrity, attenuating proinflammatory cytokine production, and promoting neural cell survival. TAM receptors also regulate the programmed cell death modes of virus-infected cells, which have profound impacts on the pathogenesis and outcome of infection. Here, we systematically review the functionalities and underlying mechanisms of TAM receptors and propose the potential application of TAM agonists to prevent severe viral encephalitis.
Topics: Animals; Mice; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Signal Transduction; Virus Diseases; c-Mer Tyrosine Kinase
PubMed: 32720213
DOI: 10.1007/s12250-020-00264-9 -
Frontiers in Immunology 2022Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due...
Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.
Topics: Arthritis, Rheumatoid; Humans; Joints; Macrophages; Quality of Life; Synovial Membrane
PubMed: 35958604
DOI: 10.3389/fimmu.2022.905356 -
PeerJ 2023Although lymphocyte-monocyte ratio (LMR) is a potential prognostic biomarker in many tumor indications, a doubt occurs around its association with head and neck squamous... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although lymphocyte-monocyte ratio (LMR) is a potential prognostic biomarker in many tumor indications, a doubt occurs around its association with head and neck squamous cell carcinoma (HNSCC). We aimed to evaluate the predictive value of LMR in patients with HNSCC.
METHODS
We searched PubMed, Web of Science, EMBASE, and the Cochrane database from inception to May 8, 2023 for systematic review and meta-analysis on LMR and outcomes related to HNSCC development. STATA software was used to estimate the correlation between LMR and prognosis. The risk ratio (hazard ratio, HR) and 95% confidence interval l (CI) for overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) were calculated, and the association between LMR and OS was further validated by subgroup analysis. The source of heterogeneity with the results of subgroup analysis was analyzed by meta-regression analysis. This meta-analysis was registered at PROSPERO (CRD42023418766).
RESULTS
After a comprehensive exploration, the results of 16 selected articles containing 5,234 subjects were evaluated. A raised LMR was connected to improved OS (HR = 1.36% CI [1.14-1.62] = 0.018), DFS (HR = 0.942, 95% CI [0.631-1.382], = 0.02), and PFS (HR = 0.932, 95% CI [0.527-1.589], < 0.022). Subgroup analysis indicated that patients with a low LMR level had a poor prognosis with a critical value of ≥4. The LMR was found to be prognostic for cases with an LMR of <4. The meta-regression analysis showed that the cut-off values and treatment methods were the primary sources of high heterogeneity in patients with HNSCC.
CONCLUSIONS
Our study suggested that an elevated LMR is a potential prognostic biomarker in patients with HNSCC and could be used to predict patient outcomes.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Monocytes; Prognosis; Lymphocytes; Head and Neck Neoplasms; Biomarkers
PubMed: 37719125
DOI: 10.7717/peerj.16014 -
Frontiers in Immunology 2024The neutrophil-to-lymphocyte ratio (NLR) is a commonly used biomarker for acute inflammation that often rises during sepsis, making it a valuable diagnostic indicator... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The neutrophil-to-lymphocyte ratio (NLR) is a commonly used biomarker for acute inflammation that often rises during sepsis, making it a valuable diagnostic indicator for clinical practice. However, no consensus has been reached on the prognostic value of NLR for predicting the prognosis and mortality risk in adult sepsis patients. In light of this controversy, we conducted a meta-analysis to clarify the prognostic significance of NLR in adult sepsis patients. The meta-analysis was registered in the PROSPERO database (registration number CRD42023433143).
METHODS
We performed a comprehensive literature search in PubMed, Cochrane Library, Ovid, and Springer databases, using retrieval terms "" or "" and "" or "" for studies published between January 1, 2000, and May 31, 2023. Children and neonates with sepsis were excluded from our research. Two independent researchers conducted the literature search and data extraction. Consensus was reached when discrepancies occurred, and in case of persistent discrepancies, the final decision was made by the research supervisor. The hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were extracted from each study included in the analysis. A random-effects model was used to synthesize all HRs and their 95% CIs. Sensitivity analysis was performed to investigate heterogeneity. Sensitivity analysis was conducted to identify studies that had a significant impact on the overall results of the meta-analysis. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. Egger's test was also used to investigate publication bias in this meta-analysis.
RESULTS
After a comprehensive literature search and screening, we included 12 studies comprising 10,811 patients for the meta-analysis. The pooled results indicated that patients with a higher NLR level were associated with a poor prognosis (Random-effects model, HR: 1.6273, 95% CI: 1.3951-1.8981). Heterogeneity testing showed significant heterogeneity (I 87.2%, 95% CI: 79.5-92, p<0.0001). Sensitivity analysis was performed to investigate the sources of heterogeneity, which revealed that the omission of one highly sensitive study significantly reduced the I value. After removing this study, a strong association was found between a higher NLR level and poor prognosis and risk of death in adult sepsis patients (Random-effects model, HR: 1.6884, 95% CI: 1.4338-1.9882). Both subgroup analysis and meta-regression indicated that the study design and testing time of NLR were sources of heterogeneity. Egger's test showed no obvious publication bias in this meta-analysis.
CONCLUSION
NLR is a reliable and valuable biomarker for predicting prognosis and the risk of death in adult sepsis patients.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433143] PROSPERO, identifier [CRD42023433143].
Topics: Child; Infant, Newborn; Humans; Neutrophils; Leukocyte Count; Lymphocytes; Prognosis; Biomarkers; Sepsis
PubMed: 38562922
DOI: 10.3389/fimmu.2024.1336456 -
BMJ Open May 2021The goal of treatment in ulcerative colitis (UC) is to induce and maintain remission. The addition of granulocyte and monocyte apheresis (GMA) to conventional therapy... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The goal of treatment in ulcerative colitis (UC) is to induce and maintain remission. The addition of granulocyte and monocyte apheresis (GMA) to conventional therapy may be a promising therapeutic alternative. In this meta-analysis, we aimed to assess the efficacy and safety profile of GMA as an adjunctive therapy.
DESIGN
Systematic review and meta-analysis.
METHODS
We searched four databases (MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials) for randomised or minimised controlled trials which discussed the impact of additional GMA therapy on clinical remission induction and clinical remission maintenance compared with conventional therapy alone. Primary outcomes were clinical remission induction and maintenance, secondary outcomes were adverse events (AEs) and steroid-sparing effect. ORs with 95% CIs were calculated. Trial Sequential Analyses were performed to adjusts for the risk of random errors in meta-analyses.
RESULTS
A total of 11 studies were eligible for meta-analysis. GMA was clearly demonstrated to induce and maintain clinical remission more effectively than conventional therapy alone (598 patients: OR: 1.93, 95% CI 1.28 to 2.91, p=0.002, I=0.0% for induction; 71 patients: OR: 8.34, 95% CI 2.64 to 26.32, p<0.001, I=0.0% for maintenance). There was no statistically significant difference in the number of AEs (OR: 0.27, 95% CI 0.05 to 1.50, p=0.135, I=84.2%).
CONCLUSION
GMA appears to be more effective as an adjunctive treatment in inducing and maintaining remission in patients with UC than conventional therapy alone.
PROSPERO REGISTRATION NUMBER
CRD42019134050.
Topics: Blood Component Removal; Colitis, Ulcerative; Granulocytes; Humans; Monocytes; Remission Induction
PubMed: 34011580
DOI: 10.1136/bmjopen-2020-042374 -
Frontiers in Immunology 2021MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can...
MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.
Topics: Animals; Antineoplastic Agents; Dendritic Cells; Disease Progression; Humans; Immunotherapy; Killer Cells, Natural; Lymphocytes, Tumor-Infiltrating; MicroRNAs; Myeloid-Derived Suppressor Cells; Neoplasms; Phenotype; Tumor Escape; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 34084160
DOI: 10.3389/fimmu.2021.624725