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Nature Reviews. Rheumatology Oct 2021Most rheumatic and musculoskeletal diseases (RMDs) can be placed along a spectrum of disorders, with autoinflammatory diseases (including monogenic systemic... (Review)
Review
Most rheumatic and musculoskeletal diseases (RMDs) can be placed along a spectrum of disorders, with autoinflammatory diseases (including monogenic systemic autoinflammatory diseases) and autoimmune diseases (such as systemic lupus erythematosus and antiphospholipid syndrome) representing the two ends of this spectrum. However, although most autoinflammatory diseases are characterized by the activation of innate immunity and inflammasomes and classical autoimmunity typically involves adaptive immune responses, there is some overlap in the features of autoimmunity and autoinflammation in RMDs. Indeed, some 'mixed-pattern' diseases such as spondyloarthritis and some forms of rheumatoid arthritis can also be delineated. A better understanding of the pathogenic pathways of autoinflammation and autoimmunity in RMDs, as well as the preferential cytokine patterns observed in these diseases, could help us to design targeted treatment strategies.
Topics: Autoimmune Diseases; Autoimmunity; Humans; Immunity, Innate; Inflammation; Musculoskeletal Diseases; Rheumatic Diseases
PubMed: 34341562
DOI: 10.1038/s41584-021-00652-9 -
Autoimmunity Reviews Nov 2017Neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membranes of activated neutrophils. NETs are found in a variety of conditions such as... (Review)
Review
Neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membranes of activated neutrophils. NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. Studies suggest that an imbalance between "NETosis," which is a process by which NETs are formed, and NET degradation may be associated with autoimmune diseases. Neutrophils, interleukin-8, ANCA and other inflammatory molecules are considered to play a key role in NET formation. Prolonged exposure to NETs-related cascades is associated with autoimmunity and increases the chance of systemic organ damage. In this review, we discuss the roles of various inflammatory molecules in relation to NETs. We also describe the role of NETs in the pathogenesis of autoimmune diseases and discuss the possibility of using targeted therapies directed to NETs and associated molecules to treat autoimmune diseases.
Topics: Autoimmune Diseases; Autoimmunity; Extracellular Traps; Humans; Neutrophils; Prognosis
PubMed: 28899799
DOI: 10.1016/j.autrev.2017.09.012 -
Current Opinion in Rheumatology Sep 2019Complement system dysfunction in terms of upregulation, downregulation, or dysregulation can create an imbalance of both host defense and inflammatory response leading... (Review)
Review
PURPOSE OF REVIEW
Complement system dysfunction in terms of upregulation, downregulation, or dysregulation can create an imbalance of both host defense and inflammatory response leading to autoimmunity. In this review, we aimed at describing the role of complement system in host defense to inflection and in autoimmunity starting from the evidence from primary and secondary complement system deficiencies.
RECENT FINDINGS
Complement system has a determinant role in defense against infections: deficiencies of complement components are associated with increased susceptibility to infections. Primary complement system deficiencies are rare disorders that predispose to both infections and autoimmune diseases. Secondary complement system deficiencies are the result of the complement system activation with consumption. Complement system role in enhancing risk of infective diseases in secondary deficiencies has been demonstrated in patients affected by systemic autoimmune disorders, mainly systemic lupus erythematosus and vasculitis.
SUMMARY
The relationship between the complement system and autoimmunity appears paradoxical as both the deficiency and the activation contribute to inducing autoimmune diseases. In these conditions, the presence of complement deposition in affected tissues, decreased levels of complement proteins, and high levels of complement activation fragments in the blood and vessels have been documented.
Topics: Autoimmune Diseases; Autoimmunity; Complement Activation; Complement System Proteins; Humans; Infections
PubMed: 31192812
DOI: 10.1097/BOR.0000000000000633 -
Nature Reviews. Drug Discovery Jan 2021Despite recent advances in the treatment of autoimmune and inflammatory diseases, unmet medical needs in some areas still exist. One of the main therapeutic approaches... (Review)
Review
Despite recent advances in the treatment of autoimmune and inflammatory diseases, unmet medical needs in some areas still exist. One of the main therapeutic approaches to alleviate dysregulated inflammation has been to target the activity of kinases that regulate production of inflammatory mediators. Small-molecule kinase inhibitors have the potential for broad efficacy, convenience and tissue penetrance, and thus often offer important advantages over biologics. However, designing kinase inhibitors with target selectivity and minimal off-target effects can be challenging. Nevertheless, immense progress has been made in advancing kinase inhibitors with desirable drug-like properties into the clinic, including inhibitors of JAKs, IRAK4, RIPKs, BTK, SYK and TPL2. This Review will address the latest discoveries around kinase inhibitors with an emphasis on clinically validated autoimmunity and inflammatory pathways.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Humans; Inflammation; Protein Kinase Inhibitors; Protein Kinases
PubMed: 33077936
DOI: 10.1038/s41573-020-0082-8 -
Methods in Molecular Biology (Clifton,... 2019The immune system in a broad sense is a mechanism that allows a living organism to discriminate between "self" and "nonself." Examples of immune systems occur in...
The immune system in a broad sense is a mechanism that allows a living organism to discriminate between "self" and "nonself." Examples of immune systems occur in multicellular organisms as simple and ancient as sea sponges. In fact, complex multicellular life would be impossible without the ability to exclude external life from the internal environment. This introduction to the immune system will explore the cell types and soluble factors involved in immune reactions, as well as their location in the body during development and maintenance. Additionally, a description of the immunological events during an innate and adaptive immune reaction to an infection will be discussed, as well as a brief introduction to autoimmunity, cancer immunity, vaccines, and immunotherapies.
Topics: Adaptive Immunity; Animals; Autoimmunity; Humans; Immune System; Inflammation
PubMed: 31364040
DOI: 10.1007/978-1-4939-9597-4_1 -
Clinical Immunology (Orlando, Fla.) Nov 2018Aging of the immune system in humans and animals is characterized by a decline in both adaptive and innate immune responses. Paradoxically, aging is also associated with... (Review)
Review
Aging of the immune system in humans and animals is characterized by a decline in both adaptive and innate immune responses. Paradoxically, aging is also associated with a state of chronic inflammation ("inflammaging") and an increased likelihood of developing autoimmune diseases. Epigenetic changes in non-dividing and dividing cells, including immune cells, due to environmental factors contribute to the inflammation and autoimmunity that characterize both the state and diseases of aging. Here, we review the epigenetic mechanisms involved in the development of immune senescence and autoimmunity in old age.
Topics: Adaptive Immunity; Aging; Autoimmune Diseases; Autoimmunity; Epigenesis, Genetic; Humans; Immunity, Innate; Immunosenescence; Inflammation
PubMed: 29654845
DOI: 10.1016/j.clim.2018.04.002 -
Pharmacological Research Oct 2015Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time.... (Review)
Review
Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future.
Topics: Adjuvants, Immunologic; Animals; Autoimmune Diseases; Autoimmunity; Humans; Vaccination; Vaccines
PubMed: 26275795
DOI: 10.1016/j.phrs.2015.08.003 -
Schizophrenia Research Sep 2016Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a recently-discovered synaptic autoimmune disorder in which auto-antibodies target NMDARs in the brain,... (Review)
Review
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a recently-discovered synaptic autoimmune disorder in which auto-antibodies target NMDARs in the brain, leading to their removal from the synapse. Patients manifest with prominent psychiatric symptoms - and in particular psychosis - early in the disease course. This presentation converges with long-standing evidence on multiple fronts supporting the glutamatergic model of schizophrenia. We review mechanisms underlying disease in anti-NMDAR encephalitis, and discuss its role in furthering our understanding of neural circuit dysfunction in schizophrenia.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoimmunity; Humans; Psychotic Disorders; Schizophrenia
PubMed: 25458857
DOI: 10.1016/j.schres.2014.10.007 -
The Journal of Allergy and Clinical... Jun 2023Autoimmunity may be a manifestation of inborn errors of immunity, specifically as part of the subgroup of primary immunodeficiency known as primary immune regulatory... (Review)
Review
Autoimmunity may be a manifestation of inborn errors of immunity, specifically as part of the subgroup of primary immunodeficiency known as primary immune regulatory disorders. However, although making a single gene diagnosis can have important implications for prognosis and management, picking patients to screen can be difficult, against a background of a high prevalence of autoimmune disease in the population. This review compares the genetics of common polygenic and rare monogenic autoimmunity, and explores the molecular mechanisms, phenotypes, and inheritance of autoimmunity associated with primary immune regulatory disorders, highlighting the emerging importance of gain-of-function and non-germline somatic mutations. A novel framework for identifying rare monogenic cases of common diseases in children is presented, highlighting important clinical and immunologic features that favor single gene disease and guides clinicians in selecting appropriate patients for genomic screening. In addition, there will be a review of autoimmunity in non-genetically defined primary immunodeficiency such as common variable immunodeficiency, and of instances where primary autoimmunity can result in clinical phenocopies of inborn errors of immunity.
Topics: Humans; Autoimmune Diseases; Immunologic Deficiency Syndromes; Autoimmunity; Common Variable Immunodeficiency
PubMed: 37119983
DOI: 10.1016/j.jaip.2023.04.018 -
Nature Reviews. Neurology Mar 2023The field of autoimmune neurology is rapidly evolving, and recent discoveries have advanced our understanding of disease aetiologies. In this article, we review the key... (Review)
Review
The field of autoimmune neurology is rapidly evolving, and recent discoveries have advanced our understanding of disease aetiologies. In this article, we review the key pathogenic mechanisms underlying the development of CNS autoimmunity. First, we review non-modifiable risk factors, such as age, sex and ethnicity, as well as genetic factors such as monogenic variants, common variants in vulnerability genes and emerging HLA associations. Second, we highlight how interactions between environmental factors and epigenetics can modify disease onset and severity. Third, we review possible disease mechanisms underlying triggers that are associated with the loss of immune tolerance with consequent recognition of self-antigens; these triggers include infections, tumours and immune-checkpoint inhibitor therapies. Fourth, we outline how advances in our understanding of the anatomy of lymphatic drainage and neuroimmune interfaces are challenging long-held notions of CNS immune privilege, with direct relevance to CNS autoimmunity, and how disruption of B cell and T cell tolerance and the passage of immune cells between the peripheral and intrathecal compartments have key roles in initiating disease activity. Last, we consider novel therapeutic approaches based on our knowledge of the immunopathogenesis of autoimmune CNS disorders.
Topics: Humans; Central Nervous System; Central Nervous System Diseases; Autoimmune Diseases; Autoimmunity; Autoantigens
PubMed: 36788293
DOI: 10.1038/s41582-023-00776-4