Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a ...meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI = 2.06, 3.92) and higher odds of death (OR = 1.39; 95% CI = 1.31, 1.47) compared to females. With few exceptions, the sex bias observed in COVID-19 is a worldwide phenomenon. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease.
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormalities within the innate and adaptive immune systems. Activation and proliferation of a wide array of immune cells ...require significant up-regulation in cellular energy metabolism, with the mitochondria playing an essential role in the initiation and maintenance of this response. This article highlights how abnormal mitochondrial function may occur in SLE and focuses on how energy metabolism, oxidative stress, and impaired mitochondrial repair play a role in the pathogenesis of the disease. How this may represent an appealing novel therapeutic target for future drug therapy in SLE also is discussed.
Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral ...immunity. SARS-CoV-2 spike glycoprotein (S)-reactive antibodies were detectable using a flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.
Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid ...dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell
gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty.
CD8
T cells are cytotoxic lymphocytes that destroy pathogen infected and malignant cells through release of cytolytic molecules and proinflammatory cytokines. Although the role of CD8
T cells in ...connective tissue diseases (CTDs) has not been explored as thoroughly as that of other immune cells, research focusing on this key component of the immune system has recently gained momentum. Aberrations in cytotoxic cell function may have implications in triggering autoimmunity and may promote tissue damage leading to exacerbation of disease. In this comprehensive review of current literature, we examine the role of CD8
T cells in systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, polymyositis, and dermatomyositis with specific focus on comparing what is known about CD8
T cell peripheral blood phenotypes, CD8
T cell function, and CD8
T cell organ-specific profiles in adult and juvenile forms of these disorders. Although, the precise role of CD8
T cells in the initiation of autoimmunity and disease progression remains to be elucidated, increasing evidence indicates that CD8
T cells are emerging as an attractive target for therapy in CTDs.
Abstract While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer ...(NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.
ObjectiveSystemic lupus erythematosus (SLE) is characterized by persistent stimulation of the adaptive immune response and oxidative stress from Reactive Oxygen Species (ROS) generation. ...Mitochondria, central to energy metabolism through Oxidative Phosphorylation (OXPHOS), are implicated in the pathogenesis of SLE. This study aimed to assess abnormal mitochondrial function and associated ROS production in the adaptive immune response of SLE patients.MethodsInitially peripheral blood mononuclear cells (PBMCs) were isolated from SLE patients (n=37) and age/sex-matched healthy controls (HC, n=20). Flow cytometry (FC) was employed to quantify mitochondrial mass and mitochondria-derived ROS generation in CD4+, CD8+, and CD19+ lymphocytes. Next, we sought to evaluate the influence of soluble serum mediators on cellular function. Healthy PBMCs were isolated and cultured with 10% serum from either SLE patients (n=17) or healthy donors (n=12), before quantify ROS with FC. To evaluate CD4+ T cell derived cytokines on cellular metabolism, following magnetic bead isolation, CD4+ T cells were stimulated with anti-CD3/CD28 for 24 hours (HC=13, SLE=13). Following this, healthy PBMCs were culture in this cellular supernatant and ROS was again quantified by FC. Finally real-time CD4+ T cell mitochondrial metabolic function was evaluated using Seahorse Respirometry MitoStress Test.ResultsWhen adjusted for mitochondrial mass, individual mitochondria-derived ROS production was markedly increased in CD4+, CD8+, and CD19+ cells in SLE when compared with HC (figure 1A). Following co-culture with donor serum, healthy PBMCs cultured with SLE serum showed significantly higher ROS generation in CD4+, CD8+ and CD19+ lymphocytes when compared with HC (figure 1B). Following co-culture with supernatant from stimulated CD4+ T cells; CD8+ and CD19+ cells cultured with SLE CD4+ T cell supernatant showed higher ROS formation than those cultured with HC CD4+ supernatant (figure 1C). Seahorse Respirometry indicated higher basal CD4+ respiration (figure 1D), increased proton leak (figure 1E), and enhanced mitochondrial ATP production (figure 1F) in SLE, suggesting closer proximity to maximal function with limited upregulation potential.ConclusionThese findings underscore the significance of abnormal immune cell metabolic pathways in SLE, highlighting potential therapeutic targets. Targeting CD4+ T cell mitochondrial dysfunction may offer a novel approach for future therapeutic intervention.Abstract P120 Figure 1
Caries are a pathological process of extracorporeal nature, characterized by demineralization of inorganic substances as well as proteolysis triggered by acids produced by bacteria present in dental ...plaque, as a result of metabolism of sugars of both external and internal origin. Periodontal disease, on the other hand, is a multifactorial degenerative disease associated with inflammation, involving a group of tissues that surround the dental cervix and root of the tooth. It is believed that one of the mechanisms in the etiopathogenesis of caries and periodontitis are disorders of local and/or general oxidative stress (OS) parameters. Numerous clinical studies have confirmed the relationship between oxidative stress markers and oral diseases. In most analyzed studies, technical and biological variability was so high that none of the markers so far has proven suitable for routine clinical use. The aim of systematic reviews of the literature is to present the existing studies on OS parameters, mainly concerning the activity of antioxidant enzymes in saliva of patients with caries and periodontitis.
The wild boar Sus scrofa is one of the widely spread ungulate species in Europe, yet the origin and genetic structure of the population inhabiting Central and Eastern Europe are not well recognized. ...We analysed 101 newly obtained sequences of complete mtDNA genomes and 548 D-loop sequences of the species and combined them with previously published data. We identified five phylogenetic clades in Europe with clear phylogeographic pattern. Two of them occurred mainly in western and central part of the continent, while the range of the third clade covered North-Eastern, Central and South-Eastern Europe. The two other clades had rather restricted distribution. In Central Europe, we identified a contact zone of three mtDNA clades. Population genetic structure reflected clear phylogeographic pattern of wild boar in this part of Europe. The contribution of lineages originating from the southern (Dinaric-Balkan) and eastern (northern cost of the Black Sea) areas to the observed phylogeographic pattern of the species in Central and Eastern Europe was larger than those from the regions located in southern France, Iberian, and Italian Peninsulas. The present work was the first mitogenomic analysis conducted in Central and Eastern Europe to study genetic diversity and structure of wild boar population.
Heart failure (HF) is one of the leading causes of death worldwide. HF results not only in cardiovascular dysfunction, but also numerous pathologies in the oral cavity and salivary glands. The ...present study is the first to evaluate whether salivary inflammatory and anti-inflammatory factors may be related with the occurrence of hyposalivation in HF patients. We also evaluated the potential of salivary biomarkers in the diagnostics of HF. The study included 30 women with HF and 30 sex- and age-matched healthy controls. We demonstrated significantly higher levels of pro-inflammatory cytokines, anti-inflammatory cytokines, Th1, Th2, Th17, chemokines and growth factors in unstimulated saliva of HF patients compared to controls. However, the results do not indicate dominance of either branch of the immune response. The concentration of selected biomarkers is significantly higher in patients with HF and salivary gland dysfunction compared to patients with normal saliva secretion and healthy subjects (IL-1β, TNF-α, IL-7, IL-13, INF-γ, IL-12, IL-15, IL-5, IL-6, IL-9, IL-17, MCP-1/CCL-2, EOTAXIN/CCL11, RANTES/CCL5, GM-CSF, VEGF, FGF basic, PDFG-BB). Multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors is highly dependent on salivary gland function, i.e. salivary flow rate, total protein content and amylase activity. Using receiver operating characteristic (ROC) analysis, we showed that salivary TNF-α, INF-γ, IL-12 and EOTAXIN/CCL11 differentiated patients with HF and hyposalivation with the highest sensitivity and specificity compared to patients with normal salivary secretion and controls. Interestingly, the content of some pro- and anti-inflammatory mediators in saliva significantly exceeds their concentration in plasma. In addition, salivary biomarker levels do not reflect their plasma content, which may suggest a different nature/severity of inflammatory changes at the central (blood) and local (salivary) levels. Although our study was purely observational, the significantly higher concentration of inflammatory parameters in saliva compared to plasma, as well as the lack of saliva-blood correlation, may suggest increased production/secretion of these compounds in salivary cells of HF patients. ROC analysis did not confirm the diagnostic utility of salivary cytokines and chemokines in the differential diagnosis of HF patients.
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