Hyperstimulation of the immune system as a cause of autoimmune diseases

2020 ◽  
Vol 75 (3) ◽  
pp. 204-213
Author(s):  
Varvara A. Ryabkova ◽  
Leonid P. Churilov ◽  
Yehuda Shoenfeld
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Genetic Basis ◽  
Threshold Model ◽  
Subsequent Development ◽  
Threshold Effect ◽  
Successful Management ◽  
Polygenic Inheritance ◽  
Autoimmune Pathology ◽  
The Common

The pathogenesis of autoimmune diseases is very complex and multi-factorial. The concept of Mosaics of Autoimmunity was introduced to the scientific community 30 years ago by Y. Shoenfeld and D.A. Isenberg, and since then new tiles to the puzzle are continuously added. This concept specifies general pathological ideas about the multifactorial threshold model for polygenic inheritance with a threshold effect by the action of a number of external causal factors as applied to the field of autoimmunology. Among the external factors that can excessively stimulate the immune system, contributing to the development of autoimmune reactions, researchers are particularly interested in chemical substances, which are widely used in pharmacology and medicine. In this review we highlight the autoimmune dynamics i.e. a multistep pathogenesis of autoimmune diseases and the subsequent development of lymphoma in some cases. In this context several issues are addressed namely, genetic basis of autoimmunity; environmental immunostimulatory risk factors; gene/environmental interaction; pre-clinical autoimmunity with the presence of autoantibodies; and the mechanisms, underlying lymphomagenesis in autoimmune pathology. We believe that understanding the common model of the pathogenesis of autoimmune diseases is the first step to their successful management.

COVID-19: a Great Mime or a Trigger Event of Autoimmune Manifestations?

2020 ◽  
Vol 16 ◽  
Author(s):  
Maria Celeste Fatone
Keyword(s):  
Autoimmune Diseases ◽  
Systemic Vasculitis ◽  
Skin Lesions ◽  
Endothelial Damage ◽  
Direct Role ◽  
Acute Interstitial Pneumonia ◽  
Trigger Event ◽  
The Common ◽  
Microvascular Inflammation ◽  
Autoimmune Phenomena

: Viruses can induce autoimmune diseases, in addition to genetic predisposition and environmental factors. Particularly, coronaviruses are mentioned among the viruses implicated in autoimmunity. Today, the world's greatest threat derives from the pandemic of a new human coronavirus, called “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), the responsible agent of coronavirus disease 2019 (COVID-19). COVID-19 originated in Wuhan, the capital of Hubei, China in December 2019 and, to date, has spread to at least 187 countries. This review focuses on autoimmune manifestations described during COVID-19, including pro-thrombothic state associated to antiphospholipid antibodies (aPL), acute interstitial pneumonia, macrophage activation syndrome, lymphocytopenia, systemic vasculitis, and autoimmune skin lesions. This offers the opportunity to highlight the pathogenetic mechanisms common to COVID19 and several autoimmune diseases, in order to identify new therapeutic targets. In a supposed preliminary pathogenetic model, SARS-CoV-2 plays a direct role in triggering widespread microthrombosis and microvascular inflammation, because it is able to induce transient aPL, endothelial damage and complement activation at the same time. Hence, endothelium might represent the common pathway in which autoimmunity and infection converge. In addition, autoimmune phenomena in COVID-19 can be explained by regulatory T cells impairment and cytokines cascade.

scholarly journals Evaluation of the performance of immunoblot and immunodot techniques used to identify autoantibodies in patients with autoimmune diseases

2021 ◽  
Vol 19 (1) ◽  
pp. 237-244
Author(s):  
Youssef EL Hassouni ◽  
Mohammed Bourhia ◽  
Ahmed Bari ◽  
Riaz Ullah ◽  
Hafiz Majid Mahmood ◽  
...  
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Indirect Immunofluorescence ◽  
Antinuclear Antibodies ◽  
Pathological Conditions ◽  
Nuclear Antigens ◽  
Significant Difference ◽  
U1 Snrnp

Abstract Autoimmune diseases are pathological conditions in which the immune system mistakenly attacks its own tissues. This study evaluates the performance of two techniques, which are identifiers of autoantibody specifics: immunoblot and immunodot. This study was conducted in 300 patients of whom 62 were tested positive for antinuclear antibodies. The patients were initially screened for antinuclear antibodies using indirect immunofluorescence. Then, the identification of specific autoantibodies such as anti-extractable nuclear antigens (ENAs) was carried out using the immunoblot and immunodot techniques. The results showed that immunoblot and immunodot did not present a significant difference in their sensitivity against anti-SSA/52, SSB, CENP-B, PCNA, U1-snRNP, Jo-1, Pm-scl, and Mi-2 (p > 0.05). However, the two techniques showed a significant difference in their sensitivity toward autoantibodies anti-DNAn, anti-histone, anti-SmD1, and anti-ds-DNA (p < 0.05). The immunoblot data were in complete accordance with the immunodot data (100%) regarding the detection of autoantibodies such as anti SSA/52, SSB, CENP-B, PCNA, U1-snRP, Jo-1, Pm-scl, and Mi-2, 80% regarding SmD1, and 75% concerning ds-DNA. We should certainly pay closer attention to the efficiency of the techniques used in the diagnosis of autoimmune diseases.

scholarly journals Endocrine Disorders in Autoimmune Rheumatological Diseases: A Focus on Thyroid Autoimmune Diseases and on the Effects of Chronic Glucocorticoid Treatment

Endocrines ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 171-184
Author(s):  
Filippo Egalini ◽  
Mirko Parasiliti Caprino ◽  
Giulia Gaggero ◽  
Vincenzo Cappiello ◽  
Jacopo Giannelli ◽  
...  
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Genetic Predisposition ◽  
Endocrine Disorders ◽  
Processed Foods ◽  
Glucocorticoid Treatment ◽  
Environmental Causes ◽  
Main Effects ◽  
Rheumatological Diseases ◽  
Iatrogenic Cushing’S Syndrome

Autoimmune rheumatological diseases’ incidence and prevalence have risen over the last decades and they are becoming increasingly important worldwide. Thyroid autoimmune diseases share with them an imbalance in the immune system that lead to a pro-inflammatory environment. Usually this is the result of a multi-factorial process. In fact, it includes not only a possible genetic predisposition, but also environmental causes like microbiota dysbiosis, diet rich in processed foods, exposure to toxicants and infections. However, many aspects are currently under study. This paper aims to examine the factors that participate in the developing of rheumatological and thyroid autoimmune diseases. Moreover, as glucocorticoids still represent a leading treatment for systemic autoimmune rheumatological diseases, our secondary aim is to summarize the main effects of glucocorticoids treatment focusing on iatrogenic Cushing’s syndrome and glucocorticoids’ withdrawal syndrome.

scholarly journals Prevalence of ACSL (rs6552828) polymorphism among runners

2019 ◽  
Vol 24 ◽  
pp. 121-128
Author(s):  
Sigal Ben-Zaken ◽  
Yoav Meckel ◽  
Dan Nemet ◽  
Alon Eliakim
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Genetic Basis ◽  
Maximal Oxygen Consumption ◽  
Professional Athletes ◽  
Distance Runners ◽  
Nucleotide Polymorphism ◽  
Long Distance ◽  
Single Nucleotide ◽  
The Common

The ACSL A/G polymorphism is associated with endurance trainability. Previous studies have demonstrated that homozygotes of the minor AA allele had a reduced maximal oxygen consumption response to training compared to the common GG allele homozygotes, and that the ACSL A/G single nucleotide polymorphism explained 6.1% of the variance in the VO2max response to endurance training. The contribution of ACSL single nucleotide polymorphism to endurance trainability was shown in nonathletes, however, its potential role in professional athletes is not clear. Moreover, the genetic basis to anaerobic trainability is even less studied. Therefore, the aim of the present study was to examine the prevalence of ACSL single nucleotide polymorphism among professional Israeli long distance runners (n=59), middle distance runners (n=31), sprinters and jumpers (n=48) and non-athletic controls (n=60). The main finding of the present study was that the ACSL1 AA genotype, previously shown to be associated with reduced endurance trainability, was not higher among sprinters and jumpers (15%) compared to middle- (16%) and long-distance runners (15%). This suggests that in contrast to previous studies indicating that the ACSL1 single nucleotide polymorphism may influence endurance trainability among non-athletic individuals, the role of this polymorphism among professional athletes is still not clear.

scholarly journals Perceptions of the Importance of Sleep in Common Cold—Two Online Questionnaire-Based Surveys

2020 ◽  
Vol 2 (5) ◽  
pp. 596-605
Author(s):  
Gill Phillipson ◽  
Sue Aspley ◽  
Ingo Fietze
Keyword(s):  
Immune System ◽  
Sleep Quality ◽  
Common Cold ◽  
Western Europe ◽  
Online Survey ◽  
Symptom Relief ◽  
Online Questionnaire ◽  
The Common ◽  
Waking Up

Abstract Sleep deprivation affects the immune system and can render subjects more susceptible to symptoms associated with the common cold. The aim of this research was to investigate cold sufferers’ and doctors’ perceptions of the role of sleep in recovery from cold/flu. An online survey of 4000 adults who had suffered from cold/flu in the previous 12 months was conducted in eight countries and an online survey of 150 doctors was conducted in Germany. Responses were collected to questions regarding aspects of life affected by, and concerns while suffering from, cold/flu symptoms including nighttime awakening and actions taken to aid recovery. Responses were also collected to questions regarding advice given to cold/flu patients and the importance of sleep. Ability to sleep well was widely reported as negatively impacted by cold/flu (mean 46.1% of respondents across eight countries), especially in Western Europe, and inability to sleep well was a frequently reported concern associated with suffering from cold/flu (21.8%). To sleep more than usual was a frequently reported action taken to feel better (40.5%). Ninety-four percent of respondents reported waking up at night because of symptoms, cough being the most frequently reported symptom to awaken respondents. There was evidence of a possible relationship between sleep quality and medication taken at night for symptom relief. Countries with the highest proportions of respondents who reported sleep to be the aspect of life most negatively affected by a cold (France, Germany and Italy) were also those with the lowest proportions of respondents who reported that taking medications at night was the most effective way of getting back to sleep after waking due to cold symptoms. The majority of doctors believed sleep helped cold/flu patients to recover faster and that a good night’s sleep was important. Sleep is widely considered to be important in promoting recovery from cold/flu. Hence, the relief of symptoms that disrupt sleep is also likely to be important for a faster recovery.

scholarly journals Extracellular Vesicles Tune the Immune System in Renal Disease: A Focus on Systemic Lupus Erythematosus, Antiphospholipid Syndrome, Thrombotic Microangiopathy and ANCA-Vasculitis

2021 ◽  
Vol 22 (8) ◽  
pp. 4194
Author(s):  
Martina Mazzariol ◽  
Giovanni Camussi ◽  
Maria Felice Brizzi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Extracellular Vesicles ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Thrombotic Microangiopathy ◽  
Coagulation Cascade ◽  
Renal Diseases ◽  
Systemic Lupus

Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. The ability of EV to modulate the immune system, the coagulation cascade, the angiogenetic process, and to drive endothelial dysfunction plays a crucial role in the pathophysiology of both autoimmune and renal diseases. Recent studies have demonstrated the involvement of EV in the control of renal homeostasis by acting as intercellular signaling molecules, mediators of inflammation and tissue regeneration. Moreover, circulating EV and urinary EV secreted by renal cells have been investigated as potential early biomarkers of renal injury. In the present review, we discuss the recent findings on the involvement of EV in autoimmunity and in renal intercellular communication. We focused on EV-mediated interaction between the immune system and the kidney in autoimmune diseases displaying common renal damage, such as antiphospholipid syndrome, systemic lupus erythematosus, thrombotic microangiopathy, and vasculitis. Although further studies are needed to extend our knowledge on EV in renal pathology, a deeper investigation of the impact of EV in kidney autoimmune diseases may also provide insight into renal biological processes. Furthermore, EV may represent promising biomarkers of renal diseases with potential future applications as diagnostic and therapeutic tools.

PSVIII-5 Genetic parameters of thrombin as a proxy for horn fly abundance in beef cattle

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 239-239
Author(s):  
Ashley S Ling ◽  
Taylor Krause ◽  
Amanda Warner ◽  
Jason Duggin ◽  
Bradley Heins ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Fixed Effects ◽  
Large Scale ◽  
Genetic Basis ◽  
Threshold Model ◽  
Economic Losses ◽  
Small Data ◽  
Horn Fly ◽  
Improvement Programs ◽  
Highest Posterior Density

Abstract Horn flies (Haematobia irritans) are a major nuisance to cattle, especially in warm, humid regions, and are estimated to cause economic losses in excess of $1 billion annually to the U.S. beef cattle industry. Variation in horn fly tolerance has been reported within and across breeds, and heritability estimates ranging between 10 and 80% show a clear genetic basis. However, collecting fly abundance phenotypes is costly and logistically demanding, which precludes large-scale implementation. Consequently, finding correlated phenotypes and endo-phenotypes that are heritable and relatively easy to measure would facilitate implementation of horn fly tolerance genetic improvement programs. Thrombin (TH), a blood coagulation precursor, has a reported association with horn fly count variation within and across cattle breeds. In this study, the genetic basis of thrombin in beef cattle was investigated. Blood samples and horn fly count were collected on 360 cows and heifers twice during the summer of 2019 (June and August). Due to uncertainty associated with assessment of horn fly abundance and thrombin and the fact that economic losses occur only when fly abundance exceeds a certain threshold, thrombin was categorized into 4 classes (1=TH &gt; 500 ng/ml; 2=250&lt; TH&lt; 500 ng/ml; 3=100&lt; TH&lt; 250 ng/ml; and 4=TH&lt; 100 ng/ml). The trait was analyzed using linear (continuous) and threshold (discrete) mixed models. Both models included farm, pregnancy status, and cow age as fixed effects and additive and permanent environment random effects. The pedigree included 642 animals. Estimates of heritability were 0.24 and 0.29 using linear and threshold models, respectively. Estimates of repeatability were slightly higher using the threshold model (0.21 vs 0.19). Despite the small data size, all estimates were non-zero based on their respective highest posterior density intervals. These results indicate reasonable genetic variation for thrombin that could be harnessed for improvement of horn fly tolerance in cattle.

scholarly journals HDAC stimulates gene expression through BRD4 availability in response to IFN and in interferonopathies

2018 ◽  
Vol 215 (12) ◽  
pp. 3194-3212 ◽  
Author(s):  
Isabelle J. Marié ◽  
Hao-Ming Chang ◽  
David E. Levy
Keyword(s):  
Autoimmune Diseases ◽  
Histone Deacetylases ◽  
Elongation Factor ◽  
Positive Function ◽  
Transcriptional Elongation ◽  
Hdac Inhibition ◽  
Transcriptional Initiation ◽  
Inducible Promoters ◽  
The Common

In contrast to the common role of histone deacetylases (HDACs) for gene repression, HDAC activity provides a required positive function for IFN-stimulated gene (ISG) expression. Here, we show that HDAC1/2 as components of the Sin3A complex are required for ISG transcriptional elongation but not for recruitment of RNA polymerase or transcriptional initiation. Transcriptional arrest by HDAC inhibition coincides with failure to recruit the epigenetic reader Brd4 and elongation factor P-TEFb due to sequestration of Brd4 on hyperacetylated chromatin. Brd4 availability is regulated by an equilibrium cycle between opposed acetyltransferase and deacetylase activities that maintains a steady-state pool of free Brd4 available for recruitment to inducible promoters. An ISG expression signature is a hallmark of interferonopathies and other autoimmune diseases. Combined inhibition of HDAC1/2 and Brd4 resolved the aberrant ISG expression detected in cells derived from patients with two inherited interferonopathies, ISG15 and USP18 deficiencies, defining a novel therapeutic approach to ISG-associated autoimmune diseases.

scholarly journals Mechanisms of the induction of autoimmunity

2005 ◽  
Vol 133 (Suppl. 1) ◽  
pp. 9-15 ◽  
Author(s):  
Marija Mostarica-Stojkovic
Keyword(s):  
Immune System ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Molecular Mimicry ◽  
The Body ◽  
Peripheral Tolerance ◽  
High Avidity ◽  
Main Function ◽  
Clonal Deletion ◽  
Genetic Traits

The main function of the immune system is to protect the body by responding to invading microorganisms. Immunologic tolerance is the basic property of the immune system that provides for self/non-self discrimination so that the immune system can protect the host from external pathogens without reacting against itself. Central tolerance is achieved by the clonal deletion of self-reactive lymphocytes expressing receptors with high avidity for self. Autoreactive lymphocytes which escaped selection in the central lymphoid organs are present in the peripheral repertoire but but are kept under control by multiple diverse peripheral tolerance mechanisms acting either directly on the self-reactive T cell (T-cell intrinsic) or indirectly via additional cells (T-cell extrinsic). Intrinsic mec hanisms include ignorance of autoantigens, anergy, phenotype skewing or activation-induced cell death of autoreactive T lymphocytes, while extrinsic mechanisms act through immature and/ or tolerogenic dendritic cells as well as different types of regulatory cells. Autoimmune diseases are associated with humoral or cell-mediated immune reactions against one or more of the body?s own constituents. Activation and clonal expansion of autoreactive lymhocytes is a crucial step in the pathogenesis of autoimmune diseases. They result from the complex interactions between genetic traits and environmental factors, among which infections are the most likely cause. Several basic mechanisms may be operating whereby an infectious agent actually induces apparent autoimmne reactivity including molecular mimicry, bystander activation, induction of costimulation, polyclonal activation, altered processing and expression of cryptic antigens. Although many questions regarding autotolerance and etiop athogenestis of autoimmunity have yet to be resolved, it is evident that multiple overlapping pathways are operative in establishing, maintaining and breaking autotolerance, as well as during the initiation, progression, and final effector phases of autoimmunity.

scholarly journals Research on Green Total Factor Productivity of Logistics Industry and its threshold effect of Environmental Regulation

2021 ◽  
Vol 235 ◽  
pp. 02022
Author(s):  
Wanchun Li
Keyword(s):  
Environmental Regulation ◽  
Total Factor Productivity ◽  
Threshold Model ◽  
Intermediate Stage ◽  
Threshold Effect ◽  
Inhibitory Effect ◽  
Regulation System ◽  
Factor Productivity ◽  
Logistics Industry ◽  
The Government

This paper is based on the input-output panel data of logistics industry in 30 provinces and regions in China from 2005 to 2017, using nonparametric DEA model to evaluate the green total factor productivity of logistics industry, and build a panel threshold model to empirically test the nonlinear impact of environmental egulation. It is found that environmental regulation has a double threshold effect on green total factor productivity of logistics industry, the estimated threshold values are 89.85 and 211.27 respectively; when environmental regulation is at a low level below 89.85, environmental regulation has a positive effect of 2.09% on green total factor productivity of logistics industry, when environmental regulation is in the intermediate stage of 89.85 to 211.27, environmental regulation has a positive improvement effect of 6.41% on green total factor productivity of logistics industry; when environmental regulation is at a higher level than 211.27, environmental regulation has a negative inhibitory effect of 1.57% on green total factor productivity of logistics industry. Based on the empirical conclusion, this paper puts forward: First, using the performance assessment as the baton to urge the local government to establish an effective environmental regulation system; second, the government should plan to guide the green transformation and upgrading of the logistics industry to avoid “one size fits all” environmental regulation.

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