107,639 research outputs found

    Infectious diseases and autoimmunity

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    Introduction: Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. Methodology: We searched PubMed, Cochrane, and Scopus without time limits for relevant articles. Results: In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity. Conclusions: Besides genetic predisposition to autoimmunity, viral and bacterial infections are known to be involved in the initiation and promotion of autoimmune diseases. These studies suggest that pathogens can trigger autoimmunity through molecular mimicry and their adjuvant effects during initiation of disease, and can promote autoimmune responses through bystander activation or epitope spreading via inflammation and/or superantigens.</br

    Emerging patterns of genetic overlap across autoimmune disorders.

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    Most of the recently identified autoimmunity loci are shared among multiple autoimmune diseases. The pattern of genetic association with autoimmune phenotypes varies, suggesting that certain subgroups of autoimmune diseases are likely to share etiological similarities and underlying mechanisms of disease. In this review, we summarize the major findings from recent studies that have sought to refine genotype-phenotype associations in autoimmune disease by identifying both shared and distinct autoimmunity loci. More specifically, we focus on information from recent genome-wide association studies of rheumatoid arthritis, ankylosing spondylitis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes and inflammatory bowel disease. Additional work in this area is warranted given both the opportunity it provides to elucidate pathogenic mechanisms in autoimmunity and its potential to inform the development of improved diagnostic and therapeutic tools for this group on complex human disorders

    Thyroid Autoimmunity as a Window to Autoimmunity: An Explanation for Sex Differences in the Prevalence of Thyroid Autoimmunity

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    Autoimmune thyroid diseases (AITDs), predominately Graves׳ disease and Hashimoto׳s thyroiditis, comprise the most common autoimmune diseases in humans. Both have the production of anti-thyroid antibody as an important aspect and both are much more prevalent in females, being at least 10 times more common than in males. Using these two clues, a hypothesis for the initiation of thyroid autoimmunity is proposed that helps to make the case that the thyroid is one of the most sensitive sites for autoimmunity and helps account for the prevalence and the observed sex differences in AITDs and associated diseases, such as type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). The primary mechanisms proposed involve the underlying state of inflammation as a result of the adipokines, especially leptin, TNF-α, and IL-6, and the receptors able to recognize pathogen-associated molecular patterns (PAMP׳s) and damage-associated molecular patterns (DAMP׳s) through Toll-like receptors (TLR) and others receptors present on thyrocytes. The adipokines are produced by adipose tissue, but have hormone-like and immune modulating properties. As the levels of leptin are significantly higher in females, an explanation for the sex difference in thyroid autoimmunity emerges. The ability of the thyrocytes to participate in innate immunity through the TLR provides an adjuvant-like signal and allows for the action of other agents, such as environmental factors, viruses, bacteria, and even stress to provide the initiation step to break tolerance to thyroid self-antigens. Seeing the thyroid as one of the most sensitive sites for autoimmunity, means that for many autoimmune disorders, if autoimmunity is present, it is likely to also be present in the thyroid – and that that condition in the thyroid was probably earlier. The evidence is seen in multiple autoimmune syndrome

    Molecular mechanisms of autoimmunity triggered by microbial infection

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    Autoimmunity can be triggered by microbial infection. In this context, the discovery of Toll-like receptors (TLRs) provides new insights and research perspectives. TLRs induce innate and adaptive antimicrobial immune responses upon exposure to common pathogen-associated molecules, including lipopeptides, lipopolysaccharides, and nucleic acids. They also have the potential, however, to trigger autoimmune disease, as has been revealed by an increasing number of experimental reports. This review summarizes important facts about TLR biology, available data on their role in autoimmunity, and potential consequences for the management of patients with autoimmune disease

    Autoimmunity and otolaryngology diseases

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    Many systemic autoimmune diseases have otolaryngology manifestations that could represent a diagnostic challenge for clinicians, as they often constitute an early sign of an otherwise asymptomatic autoimmune condition and may lead to delayed diagnosis and treatment. In other cases, otolaryngology manifestations can be overlooked in patients with previously diagnosed autoimmune diseases. The pres- ence of concomitant conditions, the heterogeneity of studies available in the literature, and the lack of randomized trials are factors that may limit the prompt diagnosis of otolaryn- gology manifestations in systemic autoimmune diseases, with underestimation of the problem and undertreatment of the related condition

    Polyubiquitin binding to ABIN1 is required to prevent autoimmunity

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    The protein ABIN1 possesses a polyubiquitin-binding domain homologous to that present in nuclear factor kappa B (NF-kappa B) essential modulator (NEMO), a component of the inhibitor of NF-kappa B (I kappa B) kinase (IKK) complex. To address the physiological significance of polyubiquitin binding, we generated knockin mice expressing the ABIN1[D485N] mutant instead of the wild-type (WT) protein. These mice developed all the hallmarks of autoimmunity, including spontaneous formation of germinal centers, isotype switching, and production of autoreactive antibodies. Autoimmunity was suppressed by crossing to MyD88(-/-) mice, demonstrating that toll-like receptor (TLR)-MyD88 signaling pathways are needed for the phenotype to develop. The B cells and myeloid cells of the ABIN1[D485N] mice showed enhanced activation of the protein kinases TAK, IKK-alpha/beta, c-Jun N-terminal kinases, and p38 alpha mitogen-activated protein kinase and produced more IL-6 and IL-12 than WT. The mutant B cells also proliferated more rapidly in response to TLR ligands. Our results indicate that the interaction of ABIN1 with polyubiquitin is required to limit the activation of TLR-MyD88 pathways and prevent autoimmunity

    Parkinson's disease: autoimmunity and neuroinflammation

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    Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and warrant further investigation
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