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International Journal of Molecular... Sep 2020Environmental factors contribute to autoimmune disease manifestation, and as regarded today, AhR has become an important factor in studies of immunomodulation. Besides... (Review)
Review
Environmental factors contribute to autoimmune disease manifestation, and as regarded today, AhR has become an important factor in studies of immunomodulation. Besides immunological aspects, AhR also plays a role in pharmacological, toxicological and many other physiological processes such as adaptive metabolism. In recent years, epigenetic mechanisms have provided new insight into gene regulation and reveal a new contribution to autoimmune disease pathogenesis. DNA methylation, histone modifications, chromatin alterations, microRNA and consequently non-genetic changes in phenotypes connect with environmental factors. Increasing data reveals AhR cross-roads with the most significant in immunology pathways. Although study on epigenetic modulations in autoimmune diseases is still not well understood, therefore future research will help us understand their pathophysiology and help to find new therapeutic strategies. Present literature review sheds the light on the common ground between remodeling chromatin compounds and autoimmune antibodies used in diagnostics. In the proposed review we summarize recent findings that describe epigenetic factors which regulate AhR activity and impact diverse immunological responses and pathological changes.
Topics: Animals; Autoimmune Diseases; Autoimmunity; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Humans; Immunomodulation; Receptors, Aryl Hydrocarbon
PubMed: 32899152
DOI: 10.3390/ijms21176404 -
World Journal of Gastroenterology Jul 2021Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer, whereas such an association with autoimmune pancreatitis (AIP) is widely debated. Due to... (Review)
Review
Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer, whereas such an association with autoimmune pancreatitis (AIP) is widely debated. Due to the rarity of the latter disorder, there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer, which do not seem to support it. However, these studies are affected by several limitations and, therefore, a link between AIP (and, specifically, type 1 AIP) and pancreatic cancer cannot be ruled out definitively on this basis. Moreover, several immunopathological aspects of type 1 AIP and, in general, immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression. In detail, Th2 immunological dominance, type 2 macrophage polarization and basophil infiltration observed in type 1 AIP, may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis, in addition to the immunosuppressive therapies that can be used in these patients.
Topics: Autoimmune Diseases; Autoimmune Pancreatitis; Diagnosis, Differential; Humans; Pancreatic Neoplasms; Pancreatitis, Chronic
PubMed: 34321847
DOI: 10.3748/wjg.v27.i25.3825 -
Seminars in Immunopathology Jul 2022Autoimmune liver diseases are a group of immune-mediated liver diseases with three distinct entities, including autoimmune hepatitis, primary biliary cholangitis, and... (Review)
Review
Autoimmune liver diseases are a group of immune-mediated liver diseases with three distinct entities, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. The interplay of genetic and environmental factors leads to the breakdown of self-tolerance, resulting in hyper-responsiveness, and auto-aggressive immune activation. Emerging evidence links autoimmune liver diseases with alterations of the commensal microbiome configuration and aberrant immune system activation by microbial signals, mainly via the gut-liver axis. Thus, the microbiome is a new frontier to deepen the pathogenetic understanding, uncover biomarkers, and inspire innovative treatments. Herein, we review the current evidence on the role of the microbiome in autoimmune liver diseases from both clinical and basic research. We highlight recent achievements and also bottlenecks and limitations. Moreover, we give an outlook on future developments and potential for clinical applications.
Topics: Autoimmune Diseases; Hepatitis, Autoimmune; Humans; Liver; Liver Diseases; Microbiota
PubMed: 35536431
DOI: 10.1007/s00281-022-00936-6 -
Journal of Proteome Research Oct 2023Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for...
Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.
Topics: Humans; Scleroderma, Systemic; Autoantibodies; Biomarkers; Autoimmunity; Autoimmune Diseases; Peptides
PubMed: 37639699
DOI: 10.1021/acs.jproteome.3c00268 -
International Journal of Molecular... Jan 2021Chronic tic disorder and Tourette syndrome are common childhood-onset neurological diseases. However, the pathophysiology underlying these disorders is unclear, and most... (Review)
Review
Chronic tic disorder and Tourette syndrome are common childhood-onset neurological diseases. However, the pathophysiology underlying these disorders is unclear, and most studies have focused on the disinhibition of the corticostriatal-thalamocortical circuit. An autoimmune dysfunction has been proposed in the pathogenetic mechanism of Tourette syndrome and related neuropsychiatric disorders such as obsessive-compulsive disorder, autism, and attention-deficit/hyperactivity disorder. This is based on evidence from animal model studies and clinical findings. Herein, we review and give an update on the clinical characteristics, clinical evidence, and genetic studies in vitro as well as animal studies regarding immune dysfunction in Tourette syndrome.
Topics: Animals; Autoimmune Diseases; Humans; Lymphocytes; Microglia; Neurons; Obsessive-Compulsive Disorder; Streptococcal Infections; Tourette Syndrome
PubMed: 33467014
DOI: 10.3390/ijms22020853 -
Autoimmunity Reviews Feb 2024Autoimmune diseases are a group of disorders resulting from an alteration of immune tolerance, characterized by the formation of autoantibodies and the consequent... (Review)
Review
Autoimmune diseases are a group of disorders resulting from an alteration of immune tolerance, characterized by the formation of autoantibodies and the consequent development of heterogeneous clinical manifestations. Diagnosing autoimmune diseases is often complicated, and the available prognostic tools are limited. Machine learning allows us to analyze large amounts of data and carry out complex calculations quickly and with minimal effort. In this work, we examine the literature focusing on the use of machine learning in the field of the main systemic (systemic lupus erythematosus and rheumatoid arthritis) and organ-specific autoimmune diseases (type 1 diabetes mellitus, autoimmune thyroid, gastrointestinal, and skin diseases). From our analysis, interesting applications of machine learning emerged for developing algorithms useful in the early diagnosis of disease or prognostic models (risk of complications, therapeutic response). Subsequent studies and the creation of increasingly rich databases to be supplied to the algorithms will eventually guide the clinician in the diagnosis, allowing intervention when the pathology is still in an early stage and immediately directing towards a correct therapeutic approach.
Topics: Humans; Machine Learning; Autoimmune Diseases; Algorithms; Prognosis
PubMed: 38081493
DOI: 10.1016/j.autrev.2023.103496 -
Medicina (Kaunas, Lithuania) Sep 2023Acquired Hemophilia A (AHA) is a rare autoimmune disorder characterized by the onset of a sudden and unexpected bleeding episode in a patient with no personal or family... (Review)
Review
Acquired Hemophilia A (AHA) is a rare autoimmune disorder characterized by the onset of a sudden and unexpected bleeding episode in a patient with no personal or family history of bleeding diathesis, and with a typical laboratory feature, i.e., a prolonged activated partial thromboplastin time that is not otherwise explained. This bleeding disorder is caused by autoantibodies directed against the coagulation factor VIII (FVIII). AHA is idiopathic in 50% of cases and is secondary to well-defined diseases in the remaining 50%. AHA affects elderly patients although it has also been observed in the post-partum period. Bleeding manifestations are heterogeneous, ranging from mild to life-threatening bleeds involving limbs and organs. Severe bleeding with a significant decrease in hemoglobin levels must be promptly and adequately treated in order to avoid a worsening of the hemorrhages and their complications. According to international recommendations, the bypass agents (i.e., activated prothrombin complex concentrate and activated recombinant factor VII) and the replacement therapy with recombinant porcine FVIII are considered as the first-line therapy for bleeding control, due to their proven clinical efficacy. Plasma-derived or recombinant FVIII concentrates could be used as second-line treatments. Emicizumab may represent a valid and interesting therapeutic option for prophylaxis of bleeding recurrences.
Topics: Humans; Animals; Swine; Aged; Hemophilia A; Hemostatics; Hemorrhage; Autoimmune Diseases
PubMed: 37893457
DOI: 10.3390/medicina59101739 -
Frontiers in Immunology 2022The etiopathogenesis of inflammatory and autoimmune diseases, including pulmonary disease, atherosclerosis, and rheumatoid arthritis, has been linked to human exposure... (Review)
Review
The etiopathogenesis of inflammatory and autoimmune diseases, including pulmonary disease, atherosclerosis, and rheumatoid arthritis, has been linked to human exposure to volatile organic compounds (VOC) present in the environment. Chronic inflammation due to immune breakdown and malfunctioning of the immune system has been projected to play a major role in the initiation and progression of autoimmune disorders. Macrophages, major phagocytes involved in the regulation of chronic inflammation, are a major target of VOC. Excessive and prolonged activation of immune cells (T and B lymphocytes) and overexpression of the master pro-inflammatory constituents [cytokine and tumor necrosis factor-alpha, together with other mediators (interleukin-6, interleukin-1, and interferon-gamma)] have been shown to play a central role in the pathogenesis of autoimmune inflammatory responses. The function and efficiency of the immune system resulting in immunostimulation and immunosuppression are a result of exogenous and endogenous factors. An autoimmune disorder is a by-product of the overproduction of these inflammatory mediators. Additionally, an excess of these toxicants helps in promoting autoimmunity through alterations in DNA methylation in CD4 T cells. The purpose of this review is to shed light on the possible role of VOC exposure in the onset and progression of autoimmune diseases.
Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Autoimmunity; Humans; Inflammation; Volatile Organic Compounds
PubMed: 35967306
DOI: 10.3389/fimmu.2022.928379 -
Viruses Jan 2023Pediatric systemic lupus erythematosus is a chronic autoimmune disorder with a highly variable course and prognosis. It results in functional abnormalities in the immune... (Review)
Review
Pediatric systemic lupus erythematosus is a chronic autoimmune disorder with a highly variable course and prognosis. It results in functional abnormalities in the immune system due to intrinsic factors and the use of immunosuppressive therapies associated with underlying comorbidities seem to increase the risk of severe COVID-19 and poor outcomes of the disease in pediatric systemic lupus erythematosus (SLE) patients. The aim of this review is to obtain a better understanding of the existing link between this new viral infection and pediatric lupus. We have analyzed the characteristics of newly diagnosed cases of pediatric SLE following COVID-19 which have been reported in the literature and which describe the impact that COVID-19 has on patients already suffering with pediatric SLE.
Topics: Humans; Child; COVID-19; Lupus Erythematosus, Systemic; Autoimmune Diseases; Immunosuppression Therapy
PubMed: 36851487
DOI: 10.3390/v15020272 -
Frontiers in Immunology 2023Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study... (Observational Study)
Observational Study
INTRODUCTION
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study aimed to assess the long-term health risks associated with G6PD deficiency.
METHODS
A retrospective cohort study was conducted using data from a national healthcare provider in Israel (Leumit Health Services). A total of 7,473 G6PD-deficient individuals were matched with 29,892 control subjects in a 1:4 ratio, based on age, gender, socioeconomic status, and ethnic groups. The exposure of interest was recorded G6PD diagnosis or positive G6PD diagnostic test. The main outcomes and measures included rates of infectious diseases, allergic conditions, and autoimmune disorders between 2002 and 2022.
RESULTS
Significantly increased rates were observed for autoimmune disorders, infectious diseases, and allergic conditions in G6PD-deficient individuals compared to the control group. Specifically, notable increases were observed for rheumatoid arthritis (odds ratio [OR] 2.41, p<0.001), systemic lupus erythematosus (OR 4.56, p<0.001), scleroderma (OR 6.87, p<0.001), pernicious anemia (OR 18.70, p<0.001), fibromyalgia (OR 1.98, p<0.001), Graves' disease (OR 1.46, p=0.001), and Hashimoto's thyroiditis (OR 1.26, p=0.001). These findings were supported by elevated rates of positive autoimmune serology and higher utilization of medications commonly used to treat autoimmune conditions in the G6PD-deficient group.
DISCUSSION
In conclusion, individuals with G6PD deficiency are at a higher risk of developing autoimmune disorders, infectious diseases, and allergic conditions. This large-scale observational study provides valuable insights into the comprehensive association between G6PD deficiency and infectious and immune-related diseases. The findings emphasize the importance of considering G6PD deficiency as a potential risk factor in clinical practice and further research is warranted to better understand the underlying mechanisms of these associations.
Topics: Humans; Arthritis, Rheumatoid; Autoimmune Diseases; Glucosephosphate Dehydrogenase Deficiency; Graves Disease; Hypersensitivity; Retrospective Studies
PubMed: 37753082
DOI: 10.3389/fimmu.2023.1232560