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Autoimmunity Reviews Apr 2024
Topics: Humans; Autoimmune Diseases; Splenectomy; Thymectomy; Autoimmunity
PubMed: 38382859
DOI: 10.1016/j.autrev.2024.103518 -
Rheumatic Diseases Clinics of North... Feb 2018Autoimmune liver diseases coexist with rheumatic disorders in approximately 30% of cases and may also share pathogenic mechanisms. Autoimmune liver diseases result from... (Review)
Review
Autoimmune liver diseases coexist with rheumatic disorders in approximately 30% of cases and may also share pathogenic mechanisms. Autoimmune liver diseases result from an immune-mediated injury of different tissues, with autoimmune hepatitis (AIH) targeting hepatocytes, and primary biliary cholangitis (PBC) and primary sclerosing cholangitis targeting cholangiocytes. Sjogren syndrome is diagnosed in 7% of AIH cases and serologic autoimmunity profiles are a common laboratory abnormality, particularly in the case of serum antimitochondrial (PBC) or anti-liver kidney microsomal antibodies (AIH). Therapeutic strategies may overlap between rheumatic and autoimmune liver diseases and practitioners should be vigilant in managing bone loss.
Topics: Autoimmunity; Diagnosis, Differential; Genetic Predisposition to Disease; Hepatitis, Autoimmune; Humans; Precision Medicine; Rheumatic Diseases
PubMed: 29149928
DOI: 10.1016/j.rdc.2017.09.008 -
Clinical Immunology (Orlando, Fla.) Sep 2016Laminins are ubiquitous constituents of the basement membranes with major architectural and functional role as supported by the fact that absence or mutations of... (Review)
Review
Laminins are ubiquitous constituents of the basement membranes with major architectural and functional role as supported by the fact that absence or mutations of laminins lead to either lethal or severely impairing phenotypes. Besides genetic defects, laminins are involved in a wide range of human diseases including cancer, infections, and inflammatory diseases, as well as autoimmune disorders. A growing body of evidence implicates several laminin chains as autoantigens in blistering skin diseases, collagenoses, vasculitis, or post-infectious autoimmunity. The current paper reviews the existing knowledge on autoimmunity against laminins referring to both experimental and clinical data, and on therapeutic implications of anti-laminin antibodies. Further investigation of relevant laminin epitopes in pathogenic autoimmunity would facilitate the development of appropriate diagnostic tools for thorough characterization of patients' antibody specificities and should decisively contribute to designing more specific therapeutic interventions.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmunity; Basement Membrane; Humans; Laminin; Mutation; Neoplasms; Skin Diseases
PubMed: 27464450
DOI: 10.1016/j.clim.2016.07.021 -
Cellular Immunology May 2019Autoimmune diseases are heterogeneous group of disorders that together represent an enormous societal and medical problem. CD4+ T cells have critical roles in the... (Review)
Review
Autoimmune diseases are heterogeneous group of disorders that together represent an enormous societal and medical problem. CD4+ T cells have critical roles in the initiation and pathogenesis of autoimmune disease. As such, modulation of T cell activity has proven to have significant therapeutic effects in multiple autoimmune settings. T cell activation is a complex process with multiple potential therapeutic targets, many of which have been successfully utilized to treat human disease. Current pharmacological treatment largely targets T cell intrinsic activities as a means of treating various autoimmune disorders. Here I review extant and potential therapeutic approaches that instead specifically target antigen presentation to CD4+ T cells as a critical checkpoint in autoimmune responses. In addition, the contribution of antigen modulation components in current therapeutic approaches is considered along with the impact of new antigen targeted treatment modalities. Finally, potential challenges are considered in the context of the potential for antigen specific targeting of the antigen presentation process.
Topics: Animals; Antigen Presentation; Antigens; Autoimmune Diseases; Autoimmunity; CD4-Positive T-Lymphocytes; Humans
PubMed: 30554782
DOI: 10.1016/j.cellimm.2018.12.006 -
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 -
Nature Reviews. Clinical Oncology Sep 2021Many tumour antigens that do not arise from cancer cell-specific mutations are targets of humoral and cellular immunity despite their expression on non-malignant cells.... (Review)
Review
Many tumour antigens that do not arise from cancer cell-specific mutations are targets of humoral and cellular immunity despite their expression on non-malignant cells. Thus, in addition to the expected ability to detect mutations and stress-associated shifts in the immunoproteome and immunopeptidome (the sum of MHC class I-bound peptides) unique to malignant cells, the immune system also recognizes antigens expressed in non-malignant cells, which can result in autoimmune reactions against non-malignant cells from the tissue of origin. These autoimmune manifestations include, among others, vitiligo, thyroiditis and paraneoplastic syndromes, concurrent with melanoma, thyroid cancer and non-small-cell lung cancer, respectively. Importantly, despite the undesirable effects of these symptoms, such events can have prognostic value and correlate with favourable disease outcomes, suggesting 'beneficial autoimmunity'. Similarly, the occurrence of dermal and endocrine autoimmune adverse events in patients receiving immune-checkpoint inhibitors can have a positive predictive value for therapeutic outcomes. Neoplasias derived from stem cells deemed 'not essential' for survival (such as melanocytes, thyroid cells and most cells in sex-specific organs) have a particularly good prognosis, perhaps because the host can tolerate autoimmune reactions that destroy tumour cells at some cost to non-malignant tissues. In this Perspective, we discuss examples of spontaneous as well as therapy-induced autoimmunity that correlate with favourable disease outcomes and make a strong case in favour of this 'beneficial autoimmunity' being important not only in patients with advanced-stage disease but also in cancer immunosurveillance.
Topics: Autoimmunity; Biomarkers, Tumor; Female; Humans; Immunologic Surveillance; Male; Neoplasms; Prognosis
PubMed: 33976418
DOI: 10.1038/s41571-021-00508-x -
Current Opinion in Immunology Dec 2018IL-6 is implicated in the development and progression of autoimmune diseases in part by influencing CD4 T cell lineage and regulation. Elevated IL-6 levels drive... (Review)
Review
IL-6 is implicated in the development and progression of autoimmune diseases in part by influencing CD4 T cell lineage and regulation. Elevated IL-6 levels drive inflammation in a wide range of autoimmune diseases, some of which are also characterized by enhanced T cell responses to IL-6. Notably, the impact of IL-6 on inflammation is contextual in nature and dependent on the cell type, cytokine milieu and tissue. Targeting the IL-6/IL-6R axis in humans has been shown to successfully ameliorate a subset of autoimmune conditions. In this review, we discuss recent studies investigating how IL-6 regulates the CD4 T cell response in the context of autoimmune disease and highlight how blocking different aspects of the IL-6 pathway is advantageous in the treatment of disease.
Topics: Animals; Autoimmune Diseases; Autoimmunity; CD4-Positive T-Lymphocytes; Humans; Inflammation; Interleukin-6
PubMed: 30248523
DOI: 10.1016/j.coi.2018.09.002 -
Journal of Autoimmunity May 2020MicroRNAs (miRNAs) are evolutionally conserved, single-stranded RNAs that regulate gene expression at the posttranscriptional level by disrupting translation. MiRNAs are... (Review)
Review
MicroRNAs (miRNAs) are evolutionally conserved, single-stranded RNAs that regulate gene expression at the posttranscriptional level by disrupting translation. MiRNAs are key players in variety of biological processes that regulate the differentiation, development and activation of immune cells in both innate and adaptive immunity. The disruption and dysfunction of miRNAs can perturb the immune response, stimulate the release of inflammatory cytokines and initiate the production of autoantibodies, and contribute to the pathogenesis of autoimmune diseases, including systemic lupus erythmatosus (SLE), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), and multiple sclerosis (MS). Accumulating studies demonstrate that miRNAs, which can be collected by noninvasive methods, have the potential to be developed as diagnostic and therapeutic biomarkers, the discovery and validation of which is essential for the improvement of disease diagnosis and clinical monitoring. Recently, with the development of detection tools, such as microarrays and NGS (Next Generation Sequencing), large amounts of miRNAs have been identified and suggest a critical role in the pathogenesis of autoimmune diseases. Several miRNAs associated diagnostic biomarkers have been developed and applied clinically, though the pharmaceutical industry is still facing challenges in commercialization and drug delivery. The development of miRNAs is less advanced for autoimmune diseases compared with cancer. However, drugs that target miRNAs have been introduced as candidates and adopted in clinical trials. This review comprehensively summarizes the differentially expressed miRNAs in several types of autoimmune diseases and discusses the role and the significance of miRNAs in clinical management. The study of miRNAs in autoimmunity promises to provide novel and broad diagnostic and therapeutic strategies for a clinical market that is still in its infancy.
Topics: Adaptive Immunity; Animals; Autoimmune Diseases; Autoimmunity; Biomarkers; Disease Management; Gene Expression Regulation; Humans; Immunity, Innate; MicroRNAs; Molecular Diagnostic Techniques
PubMed: 32184036
DOI: 10.1016/j.jaut.2020.102438 -
Mediators of Inflammation 2018
Review
Topics: Animals; Atherosclerosis; Autoimmunity; Cardiovascular Diseases; Humans; Rheumatic Diseases
PubMed: 29785171
DOI: 10.1155/2018/6730421 -
Journal of Autoimmunity May 2023Recently, it has been described that innate immune cells such as monocytes, macrophages, and natural killer cells can develop a non-specific immune response induced by... (Review)
Review
Recently, it has been described that innate immune cells such as monocytes, macrophages, and natural killer cells can develop a non-specific immune response induced by different stimuli, including lipopolysaccharides, Mycobacterium bovis Bacillus Calmette-Guérin, and oxidized low-density lipoprotein. This non-specific immune response has been named "trained immunity," whose mechanism is essential for host defense and vaccine response, promoting better infection control. However, limited information about trained immunity in other non-infectious diseases, such as autoimmune illness, has been reported. The complexity of autoimmune pathology arises from dysfunctions in the innate and adaptive immune systems, triggering different clinical outcomes depending on the disease. Nevertheless, T and B cell function dysregulation is the most common characteristic associated with autoimmunity by promoting the escape from central and peripheral tolerance. Despite the importance of adaptative immunity to autoimmune diseases, the innate immune system also plays a prominent and understudied role in these pathologies. Accordingly, epigenetic and metabolic changes associated with innate immune cells that undergo a trained process are possible new therapeutic targets for autoimmune diseases. Even so, trained immunity can be beneficial or harmful in autoimmune diseases depending on several factors associated with the stimuli. Here, we reviewed the role of trained immunity over the innate immune system and the possible role of these changes in common autoimmune diseases, including Systemic Lupus Erythematosus, Rheumatoid Arthritis, Multiple Sclerosis, and Type 1 Diabetes.
Topics: Humans; Immunity, Innate; Autoimmunity; Trained Immunity; Macrophages; Adaptive Immunity; Autoimmune Diseases
PubMed: 36526524
DOI: 10.1016/j.jaut.2022.102956