scholarly journals The Role of Exposomes in the Pathophysiology of Autoimmune Diseases I: Toxic Chemicals and Food

2021 ◽  
Vol 28 (4) ◽  
pp. 513-543
Author(s):  
Aristo Vojdani ◽  
Elroy Vojdani
Keyword(s):  
Environmental Factors ◽  
Autoimmune Diseases ◽  
Molecular Mimicry ◽  
Toxic Chemicals ◽  
Autoimmune Response ◽  
Common Mechanism ◽  
Chemical Contamination ◽  
Internal Factors ◽  
Tissue Antigens

Autoimmune diseases affect 5–9% of the world’s population. It is now known that genetics play a relatively small part in the pathophysiology of autoimmune disorders in general, and that environmental factors have a greater role. In this review, we examine the role of the exposome, an individual’s lifetime exposure to external and internal factors, in the pathophysiology of autoimmune diseases. The most common of these environmental factors are toxic chemicals, food/diet, and infections. Toxic chemicals are in our food, drink, common products, the air, and even the land we walk on. Toxic chemicals can directly damage self-tissue and cause the release of autoantigens, or can bind to human tissue antigens and form neoantigens, which can provoke autoimmune response leading to autoimmunity. Other types of autoimmune responses can also be induced by toxic chemicals through various effects at the cellular and biochemical levels. The food we eat every day commonly has colorants, preservatives, or packaging-related chemical contamination. The food itself may be antigenic for susceptible individuals. The most common mechanism for food-related autoimmunity is molecular mimicry, in which the food’s molecular structure bears a similarity with the structure of one or more self-tissues. The solution is to detect the trigger, remove it from the environment or diet, then repair the damage to the individual’s body and health.

scholarly journals Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Aristo Vojdani ◽  
Elroy Vojdani ◽  
Datis Kharrazian
Keyword(s):  
Monoclonal Antibodies ◽  
Autoimmune Diseases ◽  
Human Tissue ◽  
Molecular Mimicry ◽  
Disease Process ◽  
Cross Reactivity ◽  
Immune Reactivity ◽  
Human Tissues ◽  
Human Monoclonal Antibodies ◽  
Tissue Antigens

We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.

scholarly journals Dietary Habits Bursting into the Complex Pathogenesis of Autoimmune Diseases: The Emerging Role of Salt from Experimental and Clinical Studies

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1013 ◽  
Author(s):  
Rossana Scrivo ◽  
Carlo Perricone ◽  
Alessio Altobelli ◽  
Chiara Castellani ◽  
Lorenzo Tinti ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Clinical Studies ◽  
Dietary Habits ◽  
Salt Intake ◽  
Experimental Models ◽  
Fine Tuning ◽  
Current Evidence

The incidence and prevalence of autoimmune diseases have increased in Western countries over the last years. The pathogenesis of these disorders is multifactorial, with a combination of genetic and environmental factors involved. Since the epidemiological changes cannot be related to genetic background, which did not change significantly in that time, the role of environmental factors has been reconsidered. Among these, dietary habits, and especially an excessive salt, typical of processed foods, has been implicated in the development of autoimmune diseases. In this review, we summarize current evidence, deriving both from experimental models and clinical studies, on the capability of excessive salt intake to exacerbate proinflammatory responses affecting the pathogenesis of immune-mediated diseases. Data on several diseases are presented, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and Crohn’s disease, with many of them supporting a proinflammatory effect of salt. Likewise, a hypertonic microenvironment showed similar effects in experimental models both in vivo and in vitro. However, murine models of spontaneous autoimmune polyneuropathy exposed to high salt diet suggest opposite outcomes. These results dictate the need to further analyse the role of cooking salt in the treatment and prevention of autoimmune diseases, trying to shape a fine tuning between the possible advantages of a restricted salt intake and the changes in circulating metabolites, mediators, and hormones which come along salt consumption and could in turn influence autoimmunity.

scholarly journals The possible role of molecular mimicry in SARS-CoV-2-mediated autoimmunity: an immunobiochemical basis

2021 ◽  
Vol 90 (3) ◽  
pp. e560
Author(s):  
Dženan Kovačić ◽  
Jovana Jotanović ◽  
Jasmina Laković
Keyword(s):  
Molecular Mimicry ◽  
Causative Factor ◽  
Organ Damage ◽  
Peptide Sequence ◽  
Autoimmune Response ◽  
The Novel ◽  
Autoimmune Conditions ◽  
First Time

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), persists as a threat to global health and continues to be a rapidly evolving condition. Although COVID19 is negatively correlated with the existing comorbidities in terms of the clinical outcome, the ability of SARS-CoV-2 to mediate the novel, or to exacerbate the existing autoimmune conditions, has generated considerable interest, due to its potential implications both with regard to patients suffering from autoimmune conditions, as well as to the long-term consequences of the disease. However, although molecular mimicry has been postulated as a potential causative factor in post-COVID19 autoimmunity and multi-organ damage, a substantial body of research needs to emerge in order to achieve a more definitive conclusion. We investigated the possibility of SARS-CoV-2 peptide sequences behaving as molecular mimics with a potential to trigger an autoimmune response. Thus, on the basis of analysis in silico, we were able to develop a plausible case for the molecular mimicry as a potential aetiological mechanism of SARS-CoV-2-mediated autoimmunity, both in a multi-organ damage context or outside of the viral phase of infection. Interestingly, this is the first time that the peptide sequence of MACROD1 has been implicated in the COVID-19 autoimmunity. Additionally, we also confirm that PARP9 and PARP14 may be involved in the process.

scholarly journals SARS-COV-2 can induce an alteration of the autoimmune profile

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Maria Cristina Sacchi ◽  
Stefania Tamiazzo ◽  
Paolo Stobbione ◽  
Ernesto Cristiano Lauritano ◽  
Annalisa Roveta ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
De Novo ◽  
Clinical Chemistry ◽  
Autoimmune Response ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Autoantibody Response ◽  
Hospitalised Patients ◽  
Saccaromyces Cerevisiae

Objective: The study evaluated the autoimmune profile of COVID-19 positive hospitalised patients. Methods: 40 hospitalised patients with a confirmed diagnosis of COVID-19 were given clinical chemistry and autoimmunity tests. Results: The 40 patients enrolled in our hospital had elevated levels of common inflammatory markers such as C-Reactive Protein (CRP), Lactate Dehydrogenase (LDH) and ferritin. Interleukin-6 (IL-6) concentration was also increased, confirming the key role of this interleukin during severe acute respiratory syndrome (SARS-CoV-2) infection. The most common autoimmunity tests were performed. A significant prevalence of anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and anti-Saccaromyces cerevisiae (ASCA IgA and IgG) was found. Patients showing a de novo autoantibody response were those with a worse disease prognosis. Conclusion: Our study shows that COVID-19 infection can trigger an autoimmune response and could induce the onset of autoimmune diseases. These data explain why drugs used to treat autoimmune diseases could also be useful in combating SARS-CoV-2 infection.

TREX1 As a Potential Therapeutic Target for Autoimmune and Inflammatory Diseases

2019 ◽  
Vol 25 (30) ◽  
pp. 3239-3247 ◽  
Author(s):  
Sha-Sha Tao ◽  
Guo-Cui Wu ◽  
Qin Zhang ◽  
Tian-Ping Zhang ◽  
Rui-Xue Leng ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Therapeutic Target ◽  
Mammalian Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Autoimmune Response ◽  
Autoimmune And Inflammatory Diseases ◽  
Functional Mechanisms

Background and Objectives: The 3’ repair exonuclease 1 (TREX1) gene is the major DNA-specific 3’–5 ’exonuclease of mammalian cells which reduces single- and double-stranded DNA (ssDNA and dsDNA) to prevent undue immune activation mediated by the nucleic acid. TREX1 is also a crucial suppressor of selfrecognition that protects the host from inappropriate autoimmune activations. It has been revealed that TREX1 function is necessary to prevent host DNA accumulating after cell death which could actuate an autoimmune response. In the manuscript, we will discuss in detail the latest advancement to study the role of TREX1 in autoimmune disease. Methods: As a pivotal cytoprotective, antioxidant, anti-apoptotic, immunosuppressive, as well as an antiinflammatory molecule, the functional mechanisms of TREX1 were multifactorial. In this review, we will briefly summarize the latest advancement in studying the role of TREX1 in autoimmune disease, and discuss its potential as a therapeutic target for these diseases. Results: Deficiency of TREX1 in human patients and murine models is characterized by systemic inflammation and the disorder of TREX1 functions drives inflammatory responses leading to autoimmune disease. Moreover, much more studies revealed that mutations in TREX1 have been associated with a range of autoimmune disorders. But it is also unclear whether the mutations of TREX1 play a causal role in the disease progression, and whether manipulation of TREX1 has a beneficial effect in the treatment of autoimmune diseases. Conclusion: Integration of functional TREX1 biology into autoimmune diseases may further deepen our understanding of the development and pathogenesis of autoimmune diseases and provide new clues and evidence for the treatment of autoimmune diseases.

scholarly journals Review of Toxins Associated with Autoimmune Diseases

2021 ◽  
Author(s):  
Domina Petric
Keyword(s):  
Environmental Factors ◽  
Autoimmune Diseases ◽  
Genetic Factors ◽  
Toxic Chemicals

Aim of this article is to review the literature about the toxins that might be involved in the pathogenesis of autoimmune diseases. Almost 70% of all autoimmune diseases are caused by environmental factors, including toxic chemicals. Genetic factors contribute to approximately 30% of all autoimmune diseases.

scholarly journals Possible Implication of FcγReceptor-Mediated Trogocytosis in Susceptibility to Systemic Autoimmune Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Sakiko Masuda ◽  
Sari Iwasaki ◽  
Utano Tomaru ◽  
Tomohisa Baba ◽  
Kazuaki Katsumata ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Autoimmune Diseases ◽  
Defense Mechanism ◽  
Physiological Role ◽  
Autoimmune Response ◽  
Systemic Autoimmune Disease ◽  
Systemic Autoimmune Diseases ◽  
Cell To Cell Adhesion

Leukocytes can “gnaw away” the plasma membrane of other cells. This phenomenon, called trogocytosis, occurs subsequent to cell-to-cell adhesion. Currently, two mechanisms of trogocytosis, adhesion molecule-mediated trogocytosis and Fcγreceptor-(FcγR-) mediated trogocytosis, have been identified. In our earlier study, we established anin vitromodel of FcγR-mediated trogocytosis, namely, CD8 translocation model from T cells to neutrophils. By using this model, we demonstrated that the molecules transferred to neutrophils via FcγR-mediated trogocytosis were taken into the cytoplasm immediately. This result suggests that the chance of molecules transferred via FcγR-mediated trogocytosis to play a role on the cell surface could be time-limited. Thus, we consider the physiological role of FcγR-mediated trogocytosis as a means to remove antibodies (Abs) that bind with self-molecules rather than to extract molecules from other cells. This concept means that FcγR-mediated trogocytosis can be a defense mechanism to Ab-mediated autoimmune response. Moreover, the activity of FcγR-mediated trogocytosis was revealed to be parallel to the endocytotic activity of neutrophils, which was critically related to the susceptibility to systemic autoimmune diseases. The collective findings suggest that FcγR-mediated trogocytosis could physiologically play a role in removal of Abs bound to self-antigens and prevent autoimmune diseases.

Questions on the role of biofilms for the adaptation of microorganisms to unfavorable environmental factors by the example of P. aeruginosa

2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Environmental Factors ◽  
Barrier Function ◽  
Infectious Agent ◽  
Antagonistic Activity ◽  
The Body ◽  
Main Function ◽  
Pathogenic Potential ◽  
The Face

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.

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