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The Journal of Investigative... Jan 2018Alopecia areata (AA) is an autoimmune disorder characterized by T lymphocytic infiltrates around the bulbar region of hair follicles. Statins have surfaced as potential... (Review)
Review
Alopecia areata (AA) is an autoimmune disorder characterized by T lymphocytic infiltrates around the bulbar region of hair follicles. Statins have surfaced as potential therapeutic agents for AA, partly because of their modulation of the JAK/STAT pathway. Some data indicate that statins are a possible option for acute, but not chronic, longstanding AA. Animal studies suggest that treatment with statins increases CD4/CD25/Foxp3 populations in AA-affected mice.
Topics: Alopecia Areata; Animals; Autoimmune Diseases; Cytokines; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice; T-Lymphocytes
PubMed: 29273101
DOI: 10.1016/j.jisp.2017.10.013 -
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 -
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 -
Autoimmunity 2015Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients... (Review)
Review
Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmunity; Genetic Predisposition to Disease; Humans; LDL-Receptor Related Proteins; Myasthenia Gravis; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Receptors, Nicotinic; Thymoma
PubMed: 25915571
DOI: 10.3109/08916934.2015.1030614 -
International Journal of Epidemiology Jun 2022Attention-deficit/hyperactivity disorder (ADHD) has been associated with several autoimmune diseases (AD), both within individuals and across relatives, implying common...
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) has been associated with several autoimmune diseases (AD), both within individuals and across relatives, implying common underlying genetic or environmental factors in line with studies indicating that immunological mechanisms are key to brain development. To further elucidate the relationship between ADHD and autoimmunity we performed a population-wide familial co-aggregation study.
METHODS
We linked Swedish national registries, defined a birth cohort with their biological relatives and identified individuals diagnosed with ADHD and/or 13 ADs. The cohort included 5 178 225 individuals born between 1960 and 2010, of whom 118 927 (2.30%) had been diagnosed with ADHD. We then investigated the associations between ADHD and ADs within individuals and across relatives, with logistic regression and structural equation modelling.
RESULTS
Within individuals, ADHD was associated with a diagnosis of any of the 13 investigated ADs (adjusted odds ratio (OR) =1.34, 95% confidence interval (CI) = 1.30-1.38) as well as several specific ADs. Familial co-aggregation was observed. For example, ADHD was associated with any of the 13 ADs in mothers (OR = 1.29, 95% CI = 1.26-1.32), fathers (OR = 1.14, 95% CI = 1.11-1.18), full siblings (OR = 1.19, 95% CI = 1.15-1.22), aunts (OR = 1.12, 95% CI = 1.10-1.15), uncles (OR = 1.07, 95% CI = 1.05-1.10) and cousins (OR = 1.04, 95% CI = 1.03-1.06). Still, the absolute risks of AD among those with ADHD were low. The genetic correlation between ADHD and a diagnosis of any of the investigated ADs was 0.13 (95% CI = 0.09-0.17) and the environmental correlation was 0.02 (95% CI = -0.03-0.06).
CONCLUSIONS
We found that ADHD and ADs co-aggregate among biological relatives, indicating that the relationship between ADHD and autoimmune diseases may in part be explained by shared genetic risk factors. The patterns of familial co-aggregation of ADHD and ADs do not readily support a role of maternal immune activation in the aetiology of ADHD. The findings have implications for aetiological models of ADHD. However, screening for autoimmunity among individuals with ADHD is not warranted.
Topics: Attention Deficit Disorder with Hyperactivity; Autoimmune Diseases; Cohort Studies; Female; Humans; Mothers; Registries; Risk Factors; Sweden
PubMed: 34379767
DOI: 10.1093/ije/dyab151 -
World Journal of Gastroenterology Oct 2016Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated... (Review)
Review
Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison's disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet.
Topics: Adrenal Insufficiency; Autoimmune Diseases; Celiac Disease; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Female; Humans; Hypopituitarism; Hypothyroidism; Infertility, Female; Prevalence; Thyroiditis
PubMed: 27784959
DOI: 10.3748/wjg.v22.i38.8472 -
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 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 -
Autism Research : Official Journal of... Dec 2022The aim of this study was to examine potential synergistic effects between maternal autoimmune disease and early childhood infections and their association with autism...
The aim of this study was to examine potential synergistic effects between maternal autoimmune disease and early childhood infections and their association with autism spectrum disorder (ASD) in offspring. Both exposures have been associated with increased risk of ASD in previous studies, but potential synergistic effects remain underexplored. We conducted a population-based cohort study of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia from January 2002 to December 2008. Maternal autoimmune diagnoses and childhood infections before age 2 years were identified from linked maternal and child hospital admissions, and ASD diagnoses by age 9 years were identified from linked disability services data. Multivariable logistic regression assessed the association between each exposure and ASD and additive interaction between exposures, controlling for potential confounders. A total of 18,451 children exposed to maternal autoimmune disease were propensity score matched (1:2) to 36,902 unexposed children. Any maternal autoimmune disease (adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07-1.47) and any childhood infection before age 2 years (aOR 1.38, 95% CI 1.15-1.67) were each associated with ASD. However, there was no evidence of additive interaction between the two exposures (relative excess risk due to interaction [RERI] 0.128, 95% CI -0.418-0.675) resulting in increased odds of ASD in offspring. Future studies could examine potential interactions between other sources of maternal immune activation and childhood infection and impact on ASD and other neurodevelopmental disorders.
Topics: Child; Child, Preschool; Humans; Autism Spectrum Disorder; Cohort Studies; Odds Ratio; Logistic Models; Autoimmune Diseases
PubMed: 36189896
DOI: 10.1002/aur.2824