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Clinical and Experimental Immunology Feb 2021Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory disorder, characterized by multiorgan failure, fever and cytopenias. The diagnosis of... (Meta-Analysis)
Meta-Analysis
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory disorder, characterized by multiorgan failure, fever and cytopenias. The diagnosis of HLH and its subtype Macrophage Activation Syndrome (MAS) remains a challenge. Interleukin 18 (IL-18) is emerging as a potential biomarker for HLH/MAS but is currently not a part of diagnostic criteria. This systematic review aimed to assess the potential role of IL-18 in the diagnosis and monitoring of HLH and MAS, and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase were searched on 30 January 2020. Studies included all subtypes of HLH and a range of underlying disorders in both children and adults. A total of 14 studies were included. Generally, serum IL-18 was elevated in both primary and secondary HLH (> 1000 pg/ml) compared with other inflammatory conditions and with healthy individuals; thus, serum IL-18 may be able to discriminate between HLH and other inflammatory conditions. Significantly increased IL-18 (> 10 000 pg/ml) was also consistently described in MAS compared with other subtypes of HLH. The ability of IL-18 to distinguish MAS from systemic juvenile idiopathic arthritis (JIA) is less unambiguous, as IL-18 levels > 100 000 pg/ml were described in sJIA patients both with and without MAS. IL-18 may help to differentiate between HLH subtypes and other inflammatory conditions. As HLH and MAS are rare disorders, only few and relatively small studies exist on the subject. Larger, prospective multi-center studies are called for to assess the diagnostic precision of IL-18 for HLH and MAS.
Topics: Animals; Diagnosis, Differential; Humans; Interleukin-18; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation; Macrophage Activation Syndrome; Macrophages; Monitoring, Immunologic; Phenotype
PubMed: 33128796
DOI: 10.1111/cei.13543 -
Advances in Rheumatology (London,... Sep 2020The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a...
The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself.Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena.Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.
Topics: Age Factors; Angiotensin-Converting Enzyme 2; Animals; Antibody Formation; Betacoronavirus; Blood Coagulation Disorders; COVID-19; Comorbidity; Coronavirus Infections; Cytokine Release Syndrome; Humans; Immunity, Innate; Inflammation; Lung; Lymphopenia; Mice; Middle East Respiratory Syndrome Coronavirus; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Respiratory Distress Syndrome; Risk Factors; SARS-CoV-2; Severe Acute Respiratory Syndrome; Severity of Illness Index; Sex Factors; Virus Internalization
PubMed: 32962761
DOI: 10.1186/s42358-020-00151-7 -
Frontiers in Immunology 2019Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While macrophage models have been used to study diseases empirically, a... (Meta-Analysis)
Meta-Analysis
Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used macrophage models to perform a meta-analysis. Specifically, we obtained gene expression data from unstimulated macrophages (M0) and macrophages stimulated with lipopolysaccharides (LPS) for 2-4 h (M-LPS), LPS for 24 h (M-LPS), LPS and interferon-γ (M-LPS+IFNγ), IFNγ (M-IFNγ), interleukin-4 (M-IL4), interleukin-10 (M-IL10), and dexamethasone (M-dex). Our meta-analysis identified consistently differentially expressed genes that have been implicated in inflammatory and metabolic processes. In addition, we built macIDR, a robust classifier capable of distinguishing macrophage activation states with high accuracy (>0.95). We classified macrophages with macIDR to define their tissue- and disease-specific characteristics. We demonstrate that alveolar macrophages display high resemblance to IL10 activation, but show a drop in IFNγ signature in chronic obstructive pulmonary disease patients. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but acquired LPS-activation features in diabetic-obese patients. Rheumatoid arthritis synovial macrophages exhibit characteristics of IL10- or IFNγ-stimulation. Altogether, we defined consensus transcriptional profiles for the eight macrophage activation states, built a classification model, and demonstrated the utility of the latter for macrophages.
Topics: Arthritis, Rheumatoid; Cell Differentiation; Cytokines; Humans; Lipopolysaccharides; Macrophage Activation; Macrophages; Transcriptome
PubMed: 31921150
DOI: 10.3389/fimmu.2019.02887 -
PloS One 2019HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and...
HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.
Topics: HIV; HIV Infections; Humans; Inflammation Mediators; Respiratory System Abnormalities
PubMed: 31830103
DOI: 10.1371/journal.pone.0226347