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Frontiers in Immunology 2022Human gestation leads to a number of physiological alterations which peak at the development of placentta known for, among many other functions, being a transient but... (Review)
Review
Human gestation leads to a number of physiological alterations which peak at the development of placentta known for, among many other functions, being a transient but highly potent endocrine organ. Hormonal activity of placenta is marked by its ability to continuously produce and secrete high levels of progesterone. Progesterone guards the well-being of the fetoplacental unit throughout the gestation and one of the proposed mechanisms of this principle involves the development of local and systemic immune tolerance mainly due to impediment of CD4+ lymphocyte activation. However, though these alterations are present and well-established, autoimmunity is not entirely rare and a wide spectrum of diseases can continue, or develop , throughout the gestation or even after the delivery. Up-to-date data supports the existence of a relationship between the clinical course of chosen autoimmune diseases and levels of circulating sex steroids. The most common autoimmune endocrinopathies in pregnant women are Hashimoto's disease, Graves' disease, and, more rarely, primary adrenal insufficiency in the form of Addison's disease. Gestation can influence the clinical course of these endocrinopathies in patients who were diagnosed before conception. Multiple particles, like TSH-receptor stimulating antibodies, thyroid hormones, glucocorticoids, and anti-thyroid medications, can cross the placental barrier and evoke biological action in fetal tissues. Thyroid pathology in the form of postpartum thyroiditis is particularly prevalent in patients with positive anti-thyroperoxidase and anti-thyroglobulin antibodies. Certain populations are more at risk of developing numerous gestational complications and require regular follow-up. In our paper, we would like to address physiological, physiopathological, and clinical aspects of endocrine autoimmunity throughout human gestation, as well as special circumstances to consider in pregnant women.
Topics: Autoimmune Diseases; Autoimmunity; Female; Graves Disease; Humans; Placenta; Pregnancy; Progesterone
PubMed: 35844617
DOI: 10.3389/fimmu.2022.907561 -
Immunological Reviews Mar 2023A body of evidence has re-energized the interest on the role neutrophils in inflammatory and autoimmune conditions. For decades, neutrophils have been considered a... (Review)
Review
A body of evidence has re-energized the interest on the role neutrophils in inflammatory and autoimmune conditions. For decades, neutrophils have been considered a homogenous population. Nevertheless, accumulating evidence suggests that neutrophils are more versatile and heterogeneous than initially considered. The notion of neutrophil heterogeneity has been supported by the identification of low-density granulocytes (LDGs) in systemic lupus erythematosus (SLE) and other systemic autoimmune and autoinflammatory conditions. Transcriptomic, epigenetic, proteomic, and functional analyses support that LDGs are a distinct subset of proinflammatory neutrophils implicated in the pathogenesis of SLE and other autoimmune diseases. Importantly, it remains incompletely characterized whether LDGs detected in other inflammatory/autoimmune conditions display the same phenotype that those present in SLE. A shared feature of LDGs across diseases is their association with vascular damage, an important contributor to morbidity and mortality in chronic inflammatory conditions. Additionally, the lack of specific markers to identify LDGs in circulation or in tissue, makes it a challenge to elucidate their role in the pathogenesis of inflammatory and autoimmune conditions. In this review, we aim to examine the evidence on the biology and the putative pathogenic role of LDGs in systemic autoimmune diseases.
Topics: Humans; Autoimmunity; Proteomics; Granulocytes; Neutrophils; Lupus Erythematosus, Systemic
PubMed: 36305174
DOI: 10.1111/imr.13161 -
Cells Aug 2021Autoimmune diseases are among the most common chronic illness caused by a dysregulated immune response against self-antigens. Close to 5% of the general population in... (Review)
Review
Autoimmune diseases are among the most common chronic illness caused by a dysregulated immune response against self-antigens. Close to 5% of the general population in Western countries develops some form of autoimmunity, yet its underlying causes, although intensively studied, are still not fully known, and no curative therapies exist. It is well established that autoimmune diseases have common mechanisms and are caused by both genetic and non-genetic risk factors. One novel risk factor that can contribute to autoimmunity is somatic mutations, in a role parallel to their role in cancer. Somatic mutations are stochastic, , non-inherited mutations. In this hypothesis, the persistent proliferation of self-reactive lymphocytes (that is usually hindered by a series of checkpoints) is permitted, due to somatic mutations in these expanding cells, allowing them to bypass multiple regulatory checkpoints, causing autoimmunity. This novel concept of the contribution of these mutations in non-malignant diseases has recently started to be explored. It proposes a novel paradigm for autoimmunity etiology and could be the missing piece of the autoimmunity puzzle.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Cell Proliferation; Humans; Lymphocytes; Mutation
PubMed: 34440825
DOI: 10.3390/cells10082056 -
Frontiers in Immunology 2023MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression in ubiquitous biological processes, including immune-related pathways. This review... (Review)
Review
MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression in ubiquitous biological processes, including immune-related pathways. This review focuses on the miR-183/96/182 cluster (miR-183C), which contains three miRNAs, miR-183, -96, and -182, having almost identical seed sequences with minor differences. The similarity among seed sequences allows these three miRNAs to act cooperatively. In addition, their minor differences permit them to target distinct genes and regulate unique pathways. The expression of miR-183C was initially identified in sensory organs. Subsequently, abnormal expression of miR-183C miRNAs in various cancers and autoimmune diseases has been reported, implying their potential role in human diseases. The regulatory effects of miR-183C miRNAs on the differentiation and function of both innate and adaptive immune cells have now been documented. In this review, we have discussed the complex role of miR-183C in the immune cells in both normal and autoimmune backgrounds. We highlighted the dysregulation of miR-183C miRNAs in several autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), and ocular autoimmune disorders, and discussed the potential for utilizing miR-183C as biomarkers and therapeutic targets of specific autoimmune diseases.
Topics: Humans; Autoimmunity; Gene Expression Regulation; Autoimmune Diseases; MicroRNAs; Lupus Erythematosus, Systemic
PubMed: 36891312
DOI: 10.3389/fimmu.2023.1134634 -
Frontiers in Immunology 2022The gut microbiota plays a major role in the developmental biology and homeostasis of cells belonging to the adaptive and innate arms of the immune system. Alterations... (Review)
Review
The gut microbiota plays a major role in the developmental biology and homeostasis of cells belonging to the adaptive and innate arms of the immune system. Alterations in its composition, which are known to be regulated by both genetic and environmental factors, can either promote or suppress the pathogenic processes underlying the development of various autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes and rheumatoid arthritis, to just name a few. Cross-recognition of gut microbial antigens by autoreactive T cells as well as gut microbe-driven alterations in the activation and homeostasis of effector and regulatory T cells have been implicated in this process. Here, we summarize our current understanding of the positive and negative associations between alterations in the composition of the gut microbiota and the development of various autoimmune disorders, with a special emphasis on antigenic mimicry.
Topics: Autoimmune Diseases; Autoimmunity; Gastrointestinal Microbiome; Humans; Lupus Erythematosus, Systemic; Molecular Mimicry
PubMed: 35572569
DOI: 10.3389/fimmu.2022.873607 -
The Journal of Allergy and Clinical... Apr 2023
Topics: Humans; Autoimmunity; Autoantibodies; B-Lymphocytes
PubMed: 36813185
DOI: 10.1016/j.jaci.2023.02.008 -
International Journal of Molecular... Sep 2023Autoimmunity is defined by the presence of antibodies and/or T cells directed against self-components. Although of unknown etiology, autoimmunity commonly is associated... (Review)
Review
Autoimmunity is defined by the presence of antibodies and/or T cells directed against self-components. Although of unknown etiology, autoimmunity commonly is associated with environmental factors such as infections, which have been reported to increase the risk of developing autoimmune diseases. Occasionally, similarities between infectious non-self and self-tissue antigens may contribute to immunological cross-reactivity in autoimmune diseases. These reactions may be interpreted as molecular mimicry, which describes cross-reactivity between foreign pathogens and self-antigens that have been reported to cause tissue damage and to contribute to the development of autoimmunity. By focusing on the nature of antibodies, cross-reactivity in general, and antibody-antigen interactions, this review aims to characterize the nature of potential cross-reactive immune reactions between infectious non-self and self-tissue antigens which may be associated with autoimmunity but may not actually be the cause of disease onset.
Topics: Humans; Antibodies; Immune System Diseases; Autoimmune Diseases; Autoimmunity; Autoantigens
PubMed: 37686415
DOI: 10.3390/ijms241713609 -
Viruses Mar 2023This article provides an overview of various aspects related to post-COVID syndrome. Apart from its prevalence, symptoms and sequelae, risk determinants, and... (Review)
Review
This article provides an overview of various aspects related to post-COVID syndrome. Apart from its prevalence, symptoms and sequelae, risk determinants, and psychosocial implications, the pathogenesis of post-COVID condition is discussed in more detail. A focus on thrombo-inflammation in SARS-CoV-2 infection, the role of neutrophil extracellular traps, and the prevalence of venous thromboembolism is made. Moreover, COVID-19 and post-COVID syndrome in immunocompromising conditions, and the impact of vaccination on the prevention and treatment of post-COVID symptoms are reviewed. Autoimmunity is a hallmark of post-COVID syndrome, and, therefore, is another focus of this article. Thus, misdirected cellular and humoral immune responses can enhance the risk of latent autoimmunity in post-COVID syndrome. Facing the high prevalence of COVID-19 cases worldwide, it can be assumed that autoimmune disorders will increase globally over the next few years. Recent advances in identifying genetically determined variants may open the avenue for a better understanding of the susceptibility to and severity of SARS-CoV-2 infection and post-COVID syndrome.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Autoimmune Diseases; Autoimmunity; Disease Progression
PubMed: 36992384
DOI: 10.3390/v15030675 -
Clinical Immunology (Orlando, Fla.) Mar 2020Until recently, autoimmune disease research has primarily been focused on elucidating the role of the adaptive immune system. In the past decade or so, the role of the... (Review)
Review
Until recently, autoimmune disease research has primarily been focused on elucidating the role of the adaptive immune system. In the past decade or so, the role of the innate immune system in the pathogenesis of autoimmunity has increasingly been realized. Recent findings have elucidated paradigm-shifting concepts, for example, the implications of "trained immunity" and a dysbiotic microbiome in the susceptibility of predisposed individuals to clinical autoimmunity. In addition, the application of modern technologies such as the quantum dot (Qdot) system and 'Omics' (e.g., genomics, proteomics, and metabolomics) data-processing tools has proven fruitful in revisiting mechanisms underlying autoimmune pathogenesis and in identifying novel therapeutic targets. This review highlights recent findings discussed at the American Autoimmune Related Disease Association (AARDA) 2019 colloquium. The findings covering autoimmune diseases and autoinflammatory diseases illustrate how new developments in common innate immune pathways can contribute to the better understanding and management of these immune-mediated disorders.
Topics: Alarmins; Animals; Autoimmune Diseases; Autoimmunity; Dysbiosis; Hereditary Autoinflammatory Diseases; Humans; Immunity, Innate; Immunologic Memory; Inflammation; Microbiota; Pathogen-Associated Molecular Pattern Molecules
PubMed: 32058071
DOI: 10.1016/j.clim.2020.108361 -
Journal of Autoimmunity Sep 2023Infectious diseases are commonly implicated as potential initiators of autoimmune diseases (ADs) and represent the most commonly known factor in the development of... (Review)
Review
Infectious diseases are commonly implicated as potential initiators of autoimmune diseases (ADs) and represent the most commonly known factor in the development of autoimmunity in susceptible individuals. Epidemiological data and animal studies on multiple ADs suggest that molecular mimicry is one of the likely mechanisms for the loss of peripheral tolerance and the development of clinical disease. Besides molecular mimicry, other mechanisms such as defects in central tolerance, nonspecific bystander activation, epitope-determinant spreading, and/or constant antigenic stimuli, may also contribute for breach of tolerance and to the development of ADs. Linear peptide homology is not the only mechanism by which molecular mimicry is established. Peptide modeling (i.e., 3D structure), molecular docking analyses, and affinity estimation for HLAs are emerging as critical strategies when studying the links of molecular mimicry in the development of autoimmunity. In the current pandemic, several reports have confirmed an influence of SARS-CoV-2 on subsequent autoimmunity. Bioinformatic and experimental evidence support the potential role of molecular mimicry. Peptide dimensional analysis requires more research and will be increasingly important for designing and distributing vaccines and better understanding the role of environmental factors related to autoimmunity.
Topics: Animals; Autoimmunity; Molecular Mimicry; Molecular Docking Simulation; COVID-19; SARS-CoV-2; Autoimmune Diseases
PubMed: 37390745
DOI: 10.1016/j.jaut.2023.103070