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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 -
Translational Research : the Journal of... Jul 2022Systemic lupus erythematosus (SLE) is a chronic and often progressive autoimmune disorder marked clinically by a variable constellation of symptoms including fatigue,... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic and often progressive autoimmune disorder marked clinically by a variable constellation of symptoms including fatigue, rash, joint pains, and kidney damage. The lungs, heart, gastrointestinal system, and brain can also be impacted, and individuals with lupus are at higher risk for atherosclerosis, thrombosis, thyroid disease, and other disorders associated with chronic inflammation . Autoimmune diseases are marked by erroneous immune responses in which the target of the immune response is a "self"-antigen, or autoantigen, driven by the development of antigen-specific B or T cells that have overcome the normal systems of self-tolerance built into the development of B and T cells. SLE is specifically characterized by the production of autoantibodies against nucleic acids and their binding proteins, including anti-double stranded DNA, anti-Smith (an RNA binding protein), and many others . These antibodies bind their nuclear-derived antigens to form immune complexes that cause injury and scarring through direct deposition in tissues and activation of innate immune cells . In over 50% of SLE patients, immune complex aggregation in the kidneys drives intrarenal inflammation and injury and leads to lupus nephritis, a progressive destruction of the glomeruli that is one of the most common causes of lupus-related death . To counter this pathology increasing attention has turned to developing approaches to reduce the development and continued generation of such autoantibodies. In particular, the molecular and cellular events that lead to long term, continuous activation of such autoimmune responses have become the focus of new therapeutic strategies to limit renal and other pathologies in lupus patients. The focus of this review is to consider how the innate immune system is involved in the development and progression of lupus nephritis and how a novel approach to inhibit innate immune activation by neutralizing the activators of this response, called Damage Associated Molecular Patterns, may represent a promising approach to treat this and other autoimmune disorders.
Topics: Alarmins; Autoantibodies; Humans; Inflammation; Lupus Erythematosus, Systemic; Lupus Nephritis; Nucleic Acids
PubMed: 35245691
DOI: 10.1016/j.trsl.2022.02.007 -
International Immunopharmacology Sep 2023Celiac disease (CD) is an organ-specific autoimmune disorder that occurs in genetically predisposed individuals when exposed to exogenous dietary gluten. This exposure... (Review)
Review
Celiac disease (CD) is an organ-specific autoimmune disorder that occurs in genetically predisposed individuals when exposed to exogenous dietary gluten. This exposure to wheat gluten and related proteins from rye and barley triggers an immune response which leads to the development of enteropathy associated with symptoms of bloating, diarrhea, or malabsorption. The sole current treatment is to follow a gluten-free diet for the rest of one's life. Intestinal barriers are enriched with Unconventional T cells such as iNKT, MAIT, and γδ T cells, which lack or express only a limited range of rearranged antigen receptors. Unconventional T cells play a crucial role in regulating mucosal barrier function and microbial colonization. Unconventional T cell populations are widely represented in diseased conditions, where changes in disease activity related to iNKT and MAIT cell reduction, as well as γδ T cell expansion, are demonstrated. In this review, we discuss the role and potential employment of Unconventional T cells as a therapeutic target in the pathophysiology of celiac disease.
Topics: Humans; Celiac Disease; Glutens; Diet, Gluten-Free; Autoimmune Diseases; Diarrhea
PubMed: 37473709
DOI: 10.1016/j.intimp.2023.110666 -
Frontiers in Immunology 2023T-cell-mediated autoimmune type 1 diabetes (T1D) is characterized by the immune-mediated destruction of pancreatic beta cells (β-cells). The increasing prevalence of... (Review)
Review
T-cell-mediated autoimmune type 1 diabetes (T1D) is characterized by the immune-mediated destruction of pancreatic beta cells (β-cells). The increasing prevalence of T1D poses significant challenges to the healthcare system, particularly in countries with struggling economies. This review paper highlights the multifaceted roles of Peroxisome Proliferator-Activated Receptors (PPARs) in the context of T1D, shedding light on their potential as regulators of immune responses and β-cell biology. Recent research has elucidated the intricate interplay between CD4+ T cell subsets, such as Tregs and Th17, in developing autoimmune diseases like T1D. Th17 cells drive inflammation, while Tregs exert immunosuppressive functions, highlighting the delicate balance crucial for immune homeostasis. Immunotherapy has shown promise in reinstating self-tolerance and restricting the destruction of autoimmune responses, but further investigations are required to refine these therapeutic strategies. Intriguingly, PPARs, initially recognized for their role in lipid metabolism, have emerged as potent modulators of inflammation in autoimmune diseases, particularly in T1D. Although evidence suggests that PPARs affect the β-cell function, their influence on T-cell responses and their potential impact on T1D remains largely unexplored. It was noted that PPARα is involved in restricting the transcription of IL17A and enhancing the expression of Foxp3 by minimizing its proteasomal degradation. Thus, antagonizing PPARs may exert beneficial effects in regulating the differentiation of CD4+ T cells and preventing T1D. Therefore, this review advocates for comprehensive investigations to delineate the precise roles of PPARs in T1D pathogenesis, offering innovative therapeutic avenues that target both the immune system and pancreatic function. This review paper seeks to bridge the knowledge gap between PPARs, immune responses, and T1D, providing insights that may revolutionize the treatment landscape for this autoimmune disorder. Moreover, further studies involving PPAR agonists in non-obese diabetic (NOD) mice hold promise for developing novel T1D therapies.
Topics: Mice; Animals; Diabetes Mellitus, Type 1; Mice, Inbred NOD; Autoimmune Diseases; Cell Differentiation; Inflammation; PPAR alpha
PubMed: 37928539
DOI: 10.3389/fimmu.2023.1292238 -
Autoimmunity Reviews Nov 2023Autoimmune Lymphoproliferative Syndrome (ALPS) is an autoimmune disease that has been reported in over 2200 patients. It is a rare, genetic disease where pathogenic... (Review)
Review
Autoimmune Lymphoproliferative Syndrome (ALPS) is an autoimmune disease that has been reported in over 2200 patients. It is a rare, genetic disease where pathogenic variants occur in the extrinsic pathway of apoptosis. Various mutations in different genes, such as FAS, FASL, and CASP10, can result in ALPS. Most commonly, pathogenic variants occur in the FAS receptor. This malfunctioning pathway allows for the abnormal accumulation of lymphocytes, namely CD3 + TCRαβ+CD4 - CD8- (double negative (DN) T) cells, which are a hallmark of the disease. This disease usually presents in childhood with lymphadenopathy and splenomegaly as a result of lymphoproliferation. Over time, these patients may develop cytopenias or lymphomas because of irregularities in the immune system. Current treatments include glucocorticoids, mycophenolate mofetil, sirolimus, immunoglobulin G, and rituximab. These medications serve to manage the symptoms and there are no standardized recommendations for the management of ALPS. The only curative therapy is a bone marrow transplant, but this is rarely done because of the complications. This review serves to broaden the understanding of ALPS by discussing the mechanism of immune dysregulation, how the symptoms manifest, and the mechanisms of treatment. Additionally, we discuss the epidemiology, comorbidities, and medications relating to ALPS patients across the United States using data from Cosmos.
Topics: Humans; Autoimmune Lymphoproliferative Syndrome; Autoimmune Diseases; fas Receptor; Splenomegaly; Mutation; Sirolimus; Lymphoproliferative Disorders
PubMed: 37683818
DOI: 10.1016/j.autrev.2023.103442 -
Annals of Palliative Medicine Jan 2021At the end of the last century, genome-wide association studies revealed a significant genetic association between bipolar disorder and autoimmune diseases.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
At the end of the last century, genome-wide association studies revealed a significant genetic association between bipolar disorder and autoimmune diseases. Subsequently, the theory of immune pathogenesis of bipolar disorder gradually formed, and the research on autoimmune diseases and bipolar comorbidities began to extend to other diseases, but their correlation is still controversial. To explore the differences in the prevalence of bipolar disorder in patients with autoimmune disease and normal healthy people through meta-analysis, and to examine the relationship between bipolar disorder and autoimmune disease by reviewing the relevant literature.
METHODS
The Cochrane, PubMed, and Embase databases were searched by computer from the date of inception of the database to July 2020. The main topics of the search were based on common autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, pemphigus, and Sjogren's syndrome. The databases were comprehensively searched for controlled studies regarding the prevalence of bipolar disorder in patients with autoimmune diseases. Review Manager 5.3 software was used for meta-analysis.
RESULTS
In total, 10 cohort and case control studies were included. From these, 16 control groups were extracted based on nine autoimmune diseases. The meta-analysis demonstrated that the incidence of bipolar disorder was significantly increased in patients with autoimmune disease compared to patients without autoimmune disease, [mean difference (MD) =1.54, 95% confidence interval (CI): 1.28-1.86, P<0.00001]. Also, in the meta-analysis based on five cross-sectional analyses (in which a total of five control groups were extracted based on five autoimmune diseases), the high comorbidity rate of autoimmune diseases and bipolar disorder was verified (MD =2.23, 95% CI: 1.62-3.07, P<0.00001).
CONCLUSIONS
The prevalence of bipolar disorder is markedly higher in patients with autoimmune disease. Yet, more basic research is needed to verify the special significance of immune mechanisms in bipolar disorder.
Topics: Autoimmune Diseases; Bipolar Disorder; Cross-Sectional Studies; Genome-Wide Association Study; Humans; Prevalence
PubMed: 33440965
DOI: 10.21037/apm-20-2293 -
World Journal of Pediatrics : WJP Jul 2023Aicardi-Goutières syndrome (AGS) is a genetically determined disorder with a variable phenotype. Since the original description of AGS, advances in gene sequencing... (Review)
Review
BACKGROUND
Aicardi-Goutières syndrome (AGS) is a genetically determined disorder with a variable phenotype. Since the original description of AGS, advances in gene sequencing techniques have resulted in a significant broadening of the phenotypic spectrum associated with AGS genes, and new clinical pictures have emerged beyond the classic presentation. The aim of this review is to provide a comprehensive analysis of the clinical spectrum of AGS and report currently available treatments and new immunosuppressive strategies.
DATA SOURCES
Literature reviews and original research articles were collected from databases, including PubMed and ClinicalTrials.gov. Relevant articles about AGS were included.
RESULTS
The involvement of the nervous system certainly represents the major cause of mortality and morbidity in AGS patients. However, other clinical manifestations, such as chilblains, hepatosplenomegaly, and hematological disturbances, may lead to the diagnosis and considerably impact the prognosis and overall quality of life of these patients. Therapeutic approaches of AGS are limited to interventions aimed at specific symptoms and the management of multiple comorbidities. However, advances in understanding the pathogenesis of AGS could open new and more effective therapies.
CONCLUSIONS
The over-activation of innate immunity due to upregulated interferon production plays a critical role in AGS, leading to multi-organ damage with the main involvement of the central nervous system. To date, there is no specific and effective treatment for AGS. New drugs specifically targeting the interferon pathway may bring new hope to AGS patients.
Topics: Humans; Quality of Life; Autoimmune Diseases of the Nervous System; Nervous System Malformations; Interferons
PubMed: 36650407
DOI: 10.1007/s12519-022-00679-2 -
Neuroscience and Biobehavioral Reviews May 2022Current knowledge on the general somatic health of individuals with obsessive-compulsive disorder (OCD) is very limited. Here, we critically review the emerging... (Review)
Review
Current knowledge on the general somatic health of individuals with obsessive-compulsive disorder (OCD) is very limited. Here, we critically review the emerging literature on the topic. Rapidly accumulating evidence indicates an association between OCD and autoimmune diseases, which is not limited to streptococcus-related conditions. Similarly, an association with metabolic and circulatory system diseases has been reported, which is at least partially independent from psychiatric comorbidities and familial confounders. Preliminary results also suggest potential links with dementia, insomnia, respiratory diseases, gastrointestinal diseases, migraine, and chronic pain, but replication is warranted. The risk of death by suicide in OCD is now well established. OCD has also been associated to increased mortality due to natural causes, but more research on specific causes of death is needed. Clarification of the mechanisms behind the observed associations will be critical to inform the rational design of prevention efforts. In the meantime, while OCD symptom reduction remains a priority, clinicians should also focus on monitoring the general health and promoting healthy lifestyles of persons with OCD.
Topics: Autoimmune Diseases; Cardiovascular Diseases; Comorbidity; Humans; Morbidity; Obsessive-Compulsive Disorder
PubMed: 35271916
DOI: 10.1016/j.neubiorev.2022.104602 -
Clinical and Experimental Immunology Jul 2023Adjuvants, as the name indicates, are adjoined material aimed to assist in functioning as when added to vaccines they are meant to boost the effect and strongly... (Review)
Review
Adjuvants, as the name indicates, are adjoined material aimed to assist in functioning as when added to vaccines they are meant to boost the effect and strongly stimulate the immune system. The response of the immune system can be unpredictable, and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was developed to address possible adverse reactions of an autoimmune and inflammatory type that may be caused by adjuvants. While ASIA, as a syndrome, was coined and defined in 2011; reports describing patients with vague and nonspecific clinical symptoms following vaccinations appeared much earlier. In other words, ASIA came to define, arrange, and unite the variety of symptoms, related to autoimmunity, caused not by the vaccine itself, rather by the adjuvant part of the vaccine such as aluminum, among others. Accordingly, the introduction of ASIA enabled better understanding, proper diagnosis, and early treatment of the disorder. Furthermore, ASIA was shown to be associated with almost all body systems and various rheumatic and autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and systemic sclerosis. In addition, the correlation between COVID-19 and ASIA was noticed during the pandemic. In this review, we summarized the reported effects of adjuvants and medical literature before and after ASIA was defined, the several ways ASIA can manifest and impact different systems of the body, and the incidences of ASIA during the COVID-19 pandemic. It is important to clarify, that vaccines are among, if not the, most effective means of fighting infectious diseases however, we believe that vaccines manufacturing is not above criticism, particularly when it comes to added substances possessing a risk of side effects.
Topics: Humans; Pandemics; COVID-19; Autoimmune Diseases; Adjuvants, Immunologic; Vaccines
PubMed: 36881788
DOI: 10.1093/cei/uxad033 -
International Journal of Molecular... Oct 2023Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The... (Review)
Review
Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The pathogenesis of AITD is caused by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.
Topics: Female; Humans; Pregnancy; Hashimoto Disease; Placenta; Thyroid Diseases; Autoimmune Diseases; Graves Disease; Immunity, Innate
PubMed: 37895126
DOI: 10.3390/ijms242015442