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Clinics in Liver Disease Feb 2024Genome-wide association analyses suggest that HLA genes including HLA-DRB*0301, HLA-DRB*0401, and HLA-B*3501 as well as non-HLA genes including CD28/CTLA4/ICOS and SYNPR... (Review)
Review
Genome-wide association analyses suggest that HLA genes including HLA-DRB*0301, HLA-DRB*0401, and HLA-B*3501 as well as non-HLA genes including CD28/CTLA4/ICOS and SYNPR increased AIH susceptibility. The destruction of hepatocytes is the result of the imbalance between proinflammatory cells and immunosuppressive cells, especially the imbalance between Tregs and Th17 cells. The microbiome in patients with AIH is decreased in diversity with a specific decline in Bifidobacterium and enrichment in Veillonella and Faecalibacterium. Recent evidence has demonstrated the pathogenic role of E. gallinarum and L.reuteri in inducing autoimmunity in the liver.
Topics: Humans; Hepatitis, Autoimmune; Genome-Wide Association Study; Autoimmunity; Immunosuppressive Agents
PubMed: 37945156
DOI: 10.1016/j.cld.2023.06.003 -
Nature Reviews. Rheumatology Aug 2023Post-transcriptional regulation is a fundamental process in gene expression that has a role in diverse cellular processes, including immune responses. A core concept... (Review)
Review
Post-transcriptional regulation is a fundamental process in gene expression that has a role in diverse cellular processes, including immune responses. A core concept underlying post-transcriptional regulation is that protein abundance is not solely determined by transcript abundance. Indeed, transcription and translation are not directly coupled, and intervening steps occur between these processes, including the regulation of mRNA stability, localization and alternative splicing, which can impact protein abundance. These steps are controlled by various post-transcription factors such as RNA-binding proteins and non-coding RNAs, including microRNAs, and aberrant post-transcriptional regulation has been implicated in various pathological conditions. Indeed, studies on the pathogenesis of autoimmune and inflammatory diseases have identified various post-transcription factors as important regulators of immune cell-mediated and target effector cell-mediated pathological conditions. This Review summarizes current knowledge regarding the roles of post-transcriptional checkpoints in autoimmunity, as evidenced by studies in both haematopoietic and non-haematopoietic cells, and discusses the relevance of these findings for developing new anti-inflammatory therapies.
Topics: Humans; Autoimmunity; Gene Expression Regulation; MicroRNAs; Transcription Factors; Immunity
PubMed: 37311941
DOI: 10.1038/s41584-023-00980-y -
Neurotherapeutics : the Journal of the... Oct 2021In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune... (Review)
Review
In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune neurological disorders. Derived from thousands of healthy donors, IVIg contains IgG1 isotypes of idiotypic antibodies that have the potential to bind pathogenic autoantibodies or cross-react with various antigenic peptides, including proteins conserved among the "common cold"-pre-pandemic coronaviruses; as a result, after IVIg infusions, some of the patients' sera may transiently become positive for various neuronal antibodies, even for anti-SARS-CoV-2, necessitating caution in separating antibodies derived from the infused IVIg or acquired humoral immunity. IVIg exerts multiple effects on the immunoregulatory network by variably affecting autoantibodies, complement activation, FcRn saturation, FcγRIIb receptors, cytokines, and inflammatory mediators. Based on randomized controlled trials, IVIg is approved for the treatment of GBS, CIDP, MMN and dermatomyositis; has been effective in, myasthenia gravis exacerbations, and stiff-person syndrome; and exhibits convincing efficacy in autoimmune epilepsy, neuromyelitis, and autoimmune encephalitis. Recent evidence suggests that polymorphisms in the genes encoding FcRn and FcγRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects, impacting on individualized dosing or efficacy. For chronic maintenance therapy, IVIg and subcutaneous IgG are effective in controlled studies only in CIDP and MMN preventing relapses and axonal loss up to 48 weeks; in practice, however, IVIg is continuously used for years in all the aforementioned neurological conditions, like is a "forever necessary therapy" for maintaining stability, generating challenges on when and how to stop it. Because about 35-40% of patients on chronic therapy do not exhibit objective neurological signs of worsening after stopping IVIg but express subjective symptoms of fatigue, pains, spasms, or a feeling of generalized weakness, a conditioning effect combined with fear that discontinuing chronic therapy may destabilize a multi-year stability status is likely. The dilemmas of continuing chronic therapy, the importance of adjusting dosing and scheduling or periodically stopping IVIg to objectively assess necessity, and concerns in accurately interpreting IVIg-dependency are discussed. Finally, the merit of subcutaneous IgG, the ineffectiveness of IVIg in IgG4-neurological autoimmunities, and genetic factors affecting IVIg dosing and efficacy are addressed.
Topics: Autoantibodies; Autoimmune Diseases of the Nervous System; Autoimmunity; COVID-19; Dose-Response Relationship, Immunologic; Humans; Immunoglobulins, Intravenous; SARS-CoV-2; Treatment Outcome; Withholding Treatment
PubMed: 34766257
DOI: 10.1007/s13311-021-01108-4 -
The Journal of Investigative Dermatology Mar 2022Sex bias in immune function has been well-described, and women have been shown to counter immunologically stimulating phenomena such as infection, malignancy, and trauma... (Review)
Review
Sex bias in immune function has been well-described, and women have been shown to counter immunologically stimulating phenomena such as infection, malignancy, and trauma with more protective responses than men. Heightened immunity in women may also result in a predisposition for loss of self-tolerance and development of autoimmunity, reflected by the overwhelming female sex bias of patients with autoimmune diseases. In this review, we discuss the postulated evolutionary etiologies for sexual dimorphism in immunity. We also review the molecular mechanisms underlying divergent immune responses in men and women, including sex hormone effects, X chromosome dosage, and autosomal sex-biased genes. With increasing evidence that autoimmune disease susceptibility is influenced by numerous hormonal and genetic factors, a comprehensive understanding of these topics may facilitate the development of much-needed targeted therapeutics.
Topics: Autoimmune Diseases; Autoimmunity; Female; Humans; Male; Sex Characteristics; Sex Factors; Sexism
PubMed: 34362556
DOI: 10.1016/j.jid.2021.06.008 -
Autoimmunity Reviews Jan 2019In recent years, the cross talk between the liver and the immune system is being uncovered, in part by studying liver involvement in primary immune deficiencies (PID)... (Review)
Review
In recent years, the cross talk between the liver and the immune system is being uncovered, in part by studying liver involvement in primary immune deficiencies (PID) and in part by investigating the alterations of the immune system following orthotopic liver transplantation (OLT). Here we review some of the reciprocal interactions between the liver and the immune system. Patients with PID, particularly those involving inherited defects in T and B cells or innate immunity are prone to infections and inflammatory responses that often involve the liver. Omenn's syndrome, familial hemophagocytic lymphohistiocytosis, AIRE, FOXP3 and CD25 deficiencies, common variable immunodeficiency, CD40 ligand deficiency, chronic granulomatous disease and autoimmune lymphoproliferative syndrome are some of the notable PID associated with typical hepatobiliary abnormalities. Knowledge gained from studying these PID together with laboratory and histological evaluations can assist in managing PID-associated liver dysfunction. The liver itself also has important effects on the immune system, as evident from the growing experience with patients surviving OLT. Up to 40% of pediatric patients who receive OLT suffer from post transplantation allergy, autoimmunity, and immune-mediated disorders (PTAA). PTAA is more common after liver and heart transplantations than kidney transplantations. Potential contributing factors for the increased frequency of PTAA after OLT include the age of the patients, the prolonged use of tacrolimus and the reduced regulatory immune function with a shift towards a TH2 immune response. Better understanding of the mechanisms leading to the development of PTAA after OLT will also improve the management of these conditions.
Topics: Autoimmunity; Child; Female; Hepatitis; Humans; Liver Diseases; Liver Transplantation
PubMed: 30408587
DOI: 10.1016/j.autrev.2018.06.016 -
Frontiers of Hormone Research 2017From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis.... (Review)
Review
From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis. Endocrine and nervous systems have a pivotal role in the balancing of pro- and anti-inflammatory functions of immune system, and constitute a complex circadian neuroendocrine network. Autoimmune diseases have in fact a complex pathogenic origin in which the importance of endocrine system was demonstrated. In this chapter, we will mention the structure and function of steroidal hormones involved in the neuroendocrine immune network and we will address the ways in which endocrine and immune systems influence each other, in a bi-directional fashion. Adrenal hormones, sex hormones, vitamin D, and melatonin and prolactin importantly all contribute to the homeostasis of the immune system. Indeed, some of the steroidal hormone activities determine inhibition or stimulation of immune system components, in both physiological (i.e. suppression of an unwanted response in pregnancy, or stimulation of a protective response in infections) and pathological conditions. We will finally mention the rationale for optimization of exogenous administration of glucocorticoids in chronic autoimmune diseases, and the latest developments concerning these drugs.
Topics: Autoimmune Diseases; Autoimmunity; Humans; Immune System; Neurosecretory Systems; Steroids
PubMed: 28245457
DOI: 10.1159/000452911 -
BMC Immunology Oct 2023Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic...
Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic variation, immunological dysfunction, and various environmental factors. To improve our understanding of the mechanisms behind digestive autoimmune conditions, including factors causing gastrointestinal manifestations and pathogenesis, BMC Immunology has launched a new Collection "The digestive system and autoimmunity".
Topics: Humans; Autoimmunity; Autoimmune Diseases; Digestive System
PubMed: 37794375
DOI: 10.1186/s12865-023-00561-4 -
Nature Reviews. Immunology Feb 2023Self-reactive immune responses occur in autoimmune diseases and also in chronic inflammatory and metabolic diseases that are not generally considered as autoimmune...
Self-reactive immune responses occur in autoimmune diseases and also in chronic inflammatory and metabolic diseases that are not generally considered as autoimmune diseases. How do the mechanisms of autoreactivity in the different settings overlap and how are they distinguished? Evidence indicates that while autoimmune diseases rely on both a supportive genetic background and a cooperative environment, chronic inflammatory and metabolic diseases strongly hinge on a conducive milieu for the activation of pathogenic autoreactive cells even in the absence of facilitating polygenic factors.
Topics: Humans; Autoimmunity; Autoantibodies
PubMed: 36418434
DOI: 10.1038/s41577-022-00812-2 -
Frontiers in Immunology 2021
Topics: Animals; Autoimmunity; Bacteria; Humans; Viruses
PubMed: 34567014
DOI: 10.3389/fimmu.2021.752980 -
Immunology and Cell Biology Nov 2016A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability... (Review)
Review
A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability and chronic pain, but also lead to considerable socio-economic costs. Given that the current treatment options are not curative, have substantial side effects and a high percentage of non-responders, innovative options to the existing therapeutic armament against autoimmune diseases are urgently required. Accumulating evidence suggests that changes in the metabolism of immune cells are associated with, and contribute to the pathogenesis of autoimmunity. Additionally, some autoimmune diseases share alterations in metabolic pathways, key metabolites or metabolic byproducts such as reactive oxygen species. Other examples for metabolic changes in autoimmune settings include modifications in amino acid and cholesterol levels or glucose catabolism. Thus, the emerging field of immunometabolism may hold the potential to discover new therapeutic targets. Here, we discuss recent findings describing metabolic changes in autoimmune arthritis, multiple sclerosis as well as type 1 diabetes, focusing on pathophysiological aspects.
Topics: Animals; Autoimmunity; Humans; Metabolic Networks and Pathways; Metabolism; Models, Biological
PubMed: 27562063
DOI: 10.1038/icb.2016.77