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EBioMedicine Mar 2023Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However,...
BACKGROUND
Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However, those with co-morbidities, the elderly and immunocompromised, as well as the unvaccinated, remain disproportionately vulnerable to severe COVID-19 and its sequelae. Furthermore, as the effectiveness of vaccination wanes with time, immune escape SARS-CoV-2 variants could emerge to cause severe COVID-19. Reliable prognostic biomarkers for severe disease could be used as early indicator of re-emergence of severe COVID-19 as well as for triaging of patients for antiviral therapy.
METHODS
We performed a systematic review and re-analysis of 7 publicly available datasets, analysing a total of 140 severe and 181 mild COVID-19 patients, to determine the most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients. In addition, we included an independent cohort where blood transcriptomics of COVID-19 patients were prospectively and longitudinally monitored previously, to track the time in which these gene expression changes occur before nadir of respiratory function. Single cell RNA-sequencing of peripheral blood mononuclear cells from publicly available datasets was then used to determine the immune cell subsets involved.
FINDINGS
The most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients were MCEMP1, HLA-DRA and ETS1 across the 7 transcriptomics datasets. Moreover, we found significantly heightened MCEMP1 and reduced HLA-DRA expression as early as four days before the nadir of respiratory function, and the differential expression of MCEMP1 and HLA-DRA occurred predominantly in CD14+ cells. The online platform which we developed is publicly available at https://kuanrongchan-covid19-severity-app-t7l38g.streamlitapp.com/, for users to query gene expression differences between severe and mild COVID-19 patients in these datasets.
INTERPRETATION
Elevated MCEMP1 and reduced HLA-DRA gene expression in CD14+ cells during the early phase of disease are prognostic of severe COVID-19.
FUNDING
K.R.C is funded by the National Medical Research Council (NMRC) of Singapore under the Open Fund Individual Research Grant (MOH-000610). E.E.O. is funded by the NMRC Senior Clinician-Scientist Award (MOH-000135-00). J.G.H.L. is funded by the NMRC under the Clinician-Scientist Award (NMRC/CSAINV/013/2016-01). S.K. is funded by the NMRC under the Transition Award. This study was sponsored in part by a generous gift from The Hour Glass.
Topics: Humans; Aged; HLA-DR alpha-Chains; COVID-19; SARS-CoV-2; Leukocytes, Mononuclear; Prognosis
PubMed: 36801619
DOI: 10.1016/j.ebiom.2023.104472 -
BMC Pediatrics Jun 2023To compare the performance of Neutrophil-to-Lymphocyte Ratio (NLR) with that of Platelet-to-Lymphocyte Ratio (PLR) in diagnosing neonatal sepsis (NS). (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the performance of Neutrophil-to-Lymphocyte Ratio (NLR) with that of Platelet-to-Lymphocyte Ratio (PLR) in diagnosing neonatal sepsis (NS).
METHODS
PubMed and Embase were searched for relevant studies from the inception of the databases to May, 2022. The pooled sensitivity (SEN), specificity (SPE), and area under the receiver operator characteristic curve (AUC) were measured.
RESULTS
Thirteen studies involving 2610 participants were included. The SEN, SPE, and AUC of NLR were 0.76 (95%CI: 0.61-0.87), 0.82 (95%CI: 0.68-0.91), and 0.86 (95%CI: 0.83-0.89), respectively, and those of PLR were 0.82 (95%CI: 0.63-0.92), 0.80 (95%CI: 0.24-0.98), and 0.87 (95%CI: 0.83-0.89), respectively. Significant heterogeneity was observed among the studies. Subgroup analysis and meta-regression showed that types of sepsis (p = 0.01 for SEN), gold standard (p = 0.03 for SPE), and pre-set threshold (p<0.05 for SPE) might be the sources of heterogeneity for NLR, whereas the pre-set threshold (p<0.05 for SPE) might be the source of heterogeneity for PLR.
CONCLUSIONS
NLR and PLR would be of great accuracy for the diagnosis of NS, and the two indicators have similar diagnostic performance. However, the overall risk of bias was high, and significant heterogeneity was identified among the included studies. The results of this study should be interpreted prudently, and the normal or cut-off values and the type of sepsis should be considered. More prospective studies are needed to further support the clinical application of these findings.
Topics: Infant, Newborn; Humans; Neonatal Sepsis; Neutrophils; Sepsis; Blood Platelets; Lymphocytes
PubMed: 37391699
DOI: 10.1186/s12887-023-04094-y -
Advanced Drug Delivery Reviews 2020Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation...
Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation and differentiation of T and B cells in lymph nodes. Among many parameters impacting the resulting immune response, the presence of antigen and inflammatory cues for an appropriate temporal duration within the lymph nodes, and further within appropriate subcompartments of the lymph nodes- the right timing and location- play a critical role in shaping cellular and humoral immunity. Here we review recent advances in our understanding of how vaccine kinetics and biodistribution impact adaptive immunity, and the underlying immunological mechanisms that govern these responses. We discuss emerging approaches to engineer these properties for future vaccines, with a focus on subunit vaccines.
Topics: Adjuvants, Immunologic; B-Lymphocytes; Drug Carriers; Humans; Immunity, Humoral; Inflammation Mediators; Liposomes; Lymph Nodes; Nanoparticles; Plasmids; RNA, Messenger; T-Lymphocytes; Tissue Distribution; Vaccines
PubMed: 32598970
DOI: 10.1016/j.addr.2020.06.019 -
Frontiers in Immunology 2023Endometriosis is a chronic disease affecting 6-10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood...
BACKGROUND
Endometriosis is a chronic disease affecting 6-10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in lesion clearance in other pathologies, yet their function in endometriosis is unknown. We systematically evaluated the literature on the CD8 T in peripheral blood and endometriosis-associated tissues to determine the current understanding of their pathophysiological and clinical relevance in the disease and associated conditions (e.g. infertility and pelvic pain).
METHODS
Four databases were searched (MEDLINE, EMBASE, Web of Science, CINAHL), from database inception until September 2022, for papers written in the English language with database-specific relevant terms/free-text terms from two categories: CD8 T cells and endometriosis. We included peer-reviewed papers investigating CD8 T cells in peripheral blood and endometriosis-associated tissues of patients with surgically confirmed endometriosis between menarche and menopause, and animal models with oestrous cycles. Studies enrolling participants with other gynaecological pathologies (except uterine fibroids and tubal factor infertility used as controls), cancer, immune diseases, or taking immune or hormonal therapy were excluded.
RESULTS
28 published case-control studies and gene set analyses investigating CD8 T cells in endometriosis were included. Data consistently indicate that CD8 T cells are enriched in endometriotic lesions in comparison to eutopic endometrium, with no differences in peripheral blood CD8 T populations between patients and healthy controls. Evidence on CD8 T cells in peritoneal fluid and eutopic endometrium is conflicting. CD8 T cell cytotoxicity was increased in the menstrual effluent of patients, and genomic analyses have shown a clear trend of enriched CD8 T effector memory cells in the eutopic endometrium of patients.
CONCLUSION
Literature on CD8 T cells in endometriosis-associated tissues is inconsistent. Increased CD8 T levels are found in endometriotic lesions, however, their activation potential is understudied in all relevant tissues. Future research should focus on identifying clinically relevant phenotypes to support the development of non-invasive diagnostic and treatment strategies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier CRD42021233304.
Topics: Humans; Animals; Female; Endometriosis; Endometrium; CD8-Positive T-Lymphocytes; Infertility; Pelvic Pain
PubMed: 37497226
DOI: 10.3389/fimmu.2023.1225639 -
Frontiers in Immunology 2023Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several... (Review)
Review
Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several factors can affect the expression of glutamate receptors, playing either a tumor-promoting or tumor-suppressor role in cancer. Thus, the activation of glutamate receptors by the ligand could play a role in tumor development as ample studies have demonstrated the expression of glutamate receptors in a broad range of tumor cells. Glutamate and its receptors are involved in the regulation of different immune cells' development and function, as suggested by the receptor expression in immune cells. The activation of glutamate receptors can enhance the effectiveness of the effector's T cells, or decrease the cytokine production in immunosuppressive myeloid-derived suppressor cells, increasing the antitumor immune response. These receptors are essential for the interaction between tumor and immune cells within the tumor microenvironment (TME) and the regulation of antitumor immune responses. Although the role of glutamate in the TCA cycle has been well studied, few studies have deeply investigated the role of glutamate receptors in the regulation of cancer and immune cells within the TME. Here, by a systematic review of the available data, we will critically assess the physiopathological relevance of glutamate receptors in the regulation of cancer and immune cells in the TME and provide some unifying hypotheses for futures research on the role of glutamate receptors in the immune modulation of the tumor.
Topics: Humans; Tumor Microenvironment; Neoplasms; T-Lymphocytes; Glutamic Acid; Receptors, Glutamate
PubMed: 36817470
DOI: 10.3389/fimmu.2023.1123841 -
Current Opinion in Rheumatology Jan 2023Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent...
PURPOSE OF THE REVIEW
Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent advances in the role of Treg and interleukin (IL)-10 in the pathogenesis and treatment of systemic vasculitis, including giant cell arteritis (GCA), Takayasu arteritis, Behçet's disease, antineutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV), and cryoglobulinemia associated vasculitis.
RECENT FINDINGS
Emerging data suggest that Treg deficiencies are disease-specific, affecting distinct pathways in distinct vasculitides. Decreased peripheral blood frequencies of Treg are described in all vasculitis when compared to healthy donors. Altered Treg functions are reported in GCA, Takayasu arteritis, AAV, and Behçet's disease with different mechanisms proposed. Treatment with biologics, and sometimes other immunosuppressants, may restore Treg frequencies and/or immune activity with significant differences in active disease or disease in remission in several systemic vasculitis. IL-10 is elevated in GCA, AAV, cryoglobulinemia associated vasculitis. In Behçet's disease, IL-10 is decreased in peripheral blood and elevated in saliva. In Takayasu arteritis, IL-10 levels were essentially elevated in patients' vessel wall. Several new therapeutic approaches targeting Treg and Il-10 (low dose IL-2, CAR Treg…) are developed to treat patients with systemic vasculitis.
SUMMARY
Treg and IL-10 play a central role in the regulation of inflammation in vasculitis and new targeting approaches are emerging.
Topics: Humans; T-Lymphocytes, Regulatory; Interleukin-10; Behcet Syndrome; Giant Cell Arteritis; Takayasu Arteritis; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
PubMed: 36508306
DOI: 10.1097/BOR.0000000000000915 -
BioMed Research International 2022In light of the growing emphasis on classifying stroke patients for different levels of monitoring intensity and emergency treatments, we conducted a systematic review... (Meta-Analysis)
Meta-Analysis Review
In light of the growing emphasis on classifying stroke patients for different levels of monitoring intensity and emergency treatments, we conducted a systematic review of a wide range of clinical studies, according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, with no restrictions on the language or publication date, to analyze the potential of the neutrophil-to-lymphocyte ratio (NLR) as an early neurological deterioration (END) risk predictor. A comprehensive search was carried out in PubMed, Scopus, and Web of Science databases from the inception to March 13, 2022. Nine articles were included in our study. Stroke patients with END had significantly higher NLR levels than the those without END (SMD = 0.73; CI 95% = 0.42-1.05, value < 0.001). In the subgroup analysis, according to ethnicity, East Asian patients with END had elevated levels of NLR compared to those without END (SMD = 0.79; CI 95% = 0.52-1.06, value < 0.001). However, the difference in the Caucasian group was not significant (SMD = 0.60; CI 95% = -0.50-1.70, value = 0.28). In the subgroup analysis according to the type of stroke, the NLR levels in patients with hemorrhagic stroke who developed END were similar to those without END (SMD = 0.84, CI 95% = -0.10-1.77, value = 0.07). Vice versa, in the ischemic stroke group, patients with END had elevated levels of NLR compared to those without END (SMD = 0.67, CI 95% = 0.38-0.96, value < 0.001). NLR is a unique inflammatory biomarker whose increase in END suggests an immune system dysfunction in the pathogenesis of the disease.
Topics: Biomarkers; Humans; Lymphocytes; Neutrophils; Stroke
PubMed: 36033552
DOI: 10.1155/2022/8656864 -
Langenbeck's Archives of Surgery Feb 2023Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR),... (Meta-Analysis)
Meta-Analysis Review
Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis.
BACKGROUND
Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been proposed as useful prognostic indexes in cancer patients. However, their role in rectal cancer is controversial.
METHODS
A comprehensive literature review was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews through May 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) tool. Aim of the study was to summarize available literature on PLR, NLR, and LMR in patients with rectal cancer undergoing resection.
RESULTS
Forty-seven observational studies (14,205 patients) were included; there were 42 retrospective and 5 prospective cohort studies with an average MINORS score of 14.6 (range: 12-18). Worse overall survival was associated with high NLR (HR 1.81; 95%CI 1.52-2.15; p < 0.001), high PLR (HR 1.24; 95%CI 1.06-1.46; p = 0.009), and low LMR (HR 0.67; 95%CI 0.49-0.91; p = 0.01). High NLR and low LMR were also associated with disease-free-survival (HR 1.68; 95%CI 1.35-2.08; p < 0.001 and HR 0.71; 95%CI 0.58-0.87; p < 0.001, respectively).
CONCLUSIONS
NLR, PLR, and LMR are independent clinical predictors for overall survival in patients with rectal cancer treated with curative surgery. NLR and LMR are also good predictors for disease free survival. These biomarkers, which are readily available, appear optimal prognostic indexes and may help clinicians predict the prognosis of rectal cancer and develop individualized treatment strategies.
Topics: Humans; Prognosis; Neutrophils; Monocytes; Retrospective Studies; Prospective Studies; Lymphocytes; Biomarkers; Rectal Neoplasms
PubMed: 36781510
DOI: 10.1007/s00423-023-02786-8 -
Journal of Diabetes and Its... Apr 2022Diabetes mellitus is a state of chronic low-grade inflammation. Scavenger receptor CD163, expressed on monocyte/macrophage cells with anti-inflammatory functions, has... (Review)
Review
AIMS
Diabetes mellitus is a state of chronic low-grade inflammation. Scavenger receptor CD163, expressed on monocyte/macrophage cells with anti-inflammatory functions, has been observed in diabetes complications. This review aimed to systematically survey human studies published until 31st January 2022 for CD163 expression, in particular diabetes complications and additionally to investigate whether CD163 may be implicated as a biomarker of, and mediator in, the progression of diabetes complications.
METHODS
A systematic literature search undertaken in Scopus, Embase and Medline established 79 papers of relevance. Data extraction and assessment followed the PRISMA workflow.
RESULTS
Based on specific criteria, 11 studies totalling 821 participants were included in this review. CD163 was quantified in various forms including soluble, cell surface, and mRNA measures. This review found that soluble CD163 was upregulated in diabetes complications in various local body fluids and systemically in plasma or serum and therefore implicated in the progression of those complications. CD163+ cells and mRNA were variably expressed across diabetes complications.
CONCLUSIONS
CD163 was altered in series of diabetes complications and the circulating sCD163 has potential utility as an inflammation biomarker. The variable expression of CD163 on cell surfaces and its mRNA across different diabetes complications warrants further systematic investigation.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Diabetes Complications; Diabetes Mellitus; Humans; Inflammation; Monocytes; RNA, Messenger; Receptors, Cell Surface
PubMed: 35190247
DOI: 10.1016/j.jdiacomp.2022.108150 -
Critical Reviews in Oncology/hematology Jan 2023This study reviewed the prognostic effect of tumor-infiltrating B lymphocytes (TIBLs) on solid malignancies, to determine the potential role of TIBLs in predicting... (Meta-Analysis)
Meta-Analysis Review
This study reviewed the prognostic effect of tumor-infiltrating B lymphocytes (TIBLs) on solid malignancies, to determine the potential role of TIBLs in predicting cancer patient's prognosis and their response to immunotherapy. A total of 45 original papers involving 11,099 individual patients were included in this meta-analysis covering 7 kinds of cancer. The pooled results suggested that high levels of TIBLs were correlated with favorable OS in lung, esophageal, gastric, colorectal, liver, and breast cancer; improved RFS in lung cancer; and improved DFS in gastrointestinal neoplasms. Additionally, TIBLs were significantly correlated with negative lymphatic invasion in gastric cancer, small tumor size in hepatocellular carcinoma, and negative distant metastasis in colorectal cancer. Additionally, TIBLs were reported as a discriminative feature of patients treated with immunotherapy with improved survival. We concluded that TIBLs play a favorable prognostic role among the common solid malignancie, providing theoretical evidence for further prognosis prediction for solid tumors.
Topics: Humans; Female; Prognosis; B-Lymphocyte Subsets; Carcinoma, Hepatocellular; Breast Neoplasms; Liver Neoplasms; Lymphocytes, Tumor-Infiltrating
PubMed: 36481308
DOI: 10.1016/j.critrevonc.2022.103893