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Seminars in Immunopathology Jan 2011Type 1 diabetes (T1D) is considered a disorder whose pathogenesis is autoimmune in origin, a notion drawn in large part from studies of human pancreata performed as far... (Review)
Review
Type 1 diabetes (T1D) is considered a disorder whose pathogenesis is autoimmune in origin, a notion drawn in large part from studies of human pancreata performed as far back as the 1960s. While studies of the genetics, epidemiology, and peripheral immunity in T1D have been subject to widespread analysis over the ensuing decades, efforts to understand the disorder through analysis of human pancreata have been far more limited. We have reviewed the published literature pertaining to the pathology of the human pancreas throughout all stages in the natural history of T1D. This effort uncovered a series of findings that challenge many dogmas ascribed to T1D and revealed data suggesting the marked heterogeneity in terms of its pathology. An improved understanding and appreciation for pancreatic pathology in T1D could lead to improved disease classification, an understanding of why the disorder occurs, and better therapies for disease prevention and management.
Topics: Animals; Autoimmune Diseases; Diabetes Mellitus, Type 1; Disease Models, Animal; Humans; Insulin-Secreting Cells; Pancreas
PubMed: 20495921
DOI: 10.1007/s00281-010-0208-x -
Clinics in Dermatology 2012Scoring systems are used to assess the severity of a disease and the response to treatment. The main severity scoring indexes are the Autoimmune Bullous Skin Disorder... (Review)
Review
Scoring systems are used to assess the severity of a disease and the response to treatment. The main severity scoring indexes are the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI). They have been validated and are already used in the evaluation of pemphigus and in clinical trials. They quantify disease severity by performing a global assessment of all lesions. In recent years, other severity scoring systems have been developed for pemphigus and other autoimmune blistering diseases.
Topics: Autoimmune Diseases; Dermatology; Humans; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Skin Diseases, Vesiculobullous
PubMed: 22137234
DOI: 10.1016/j.clindermatol.2011.03.017 -
Revista Medica de Chile Mar 2019Acquired hemophilia A (AHA) is a rare and life-threatening autoimmune hemorrhagic disorder where autoantibodies are developed against factor VIII. An early diagnosis is... (Review)
Review
Acquired hemophilia A (AHA) is a rare and life-threatening autoimmune hemorrhagic disorder where autoantibodies are developed against factor VIII. An early diagnosis is challenging and mandatory: an immediate hemostatic control is required to reduce morbidity and mortality. Laboratory features of AHA are: presence of autoantibodies against factor VIII, prolonged activated partial thromboplastin time (with normal prothrombin time and thrombin time) and decreased factor VIII levels. In some cases, the results of laboratory tests may be incorrect due to errors in analysis, blood extraction or manipulation of samples; also worth of consideration are limitations in the measurement range and low sensitivity of the tests. This review highlights the importance of adequate screening in patients with suspected AHA to make an adequate diagnosis and reduce overall fatal outcomes.
Topics: Autoantibodies; Autoimmune Diseases; Blood Coagulation Tests; Early Diagnosis; Factor VIII; Hemophilia A; Humans; Partial Thromboplastin Time
PubMed: 31344171
DOI: 10.4067/S0034-98872019000300334 -
International Journal of Molecular... Jun 2014AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents... (Review)
Review
AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently.
Topics: Animals; Autoimmune Diseases; CD4-Positive T-Lymphocytes; Drug Discovery; Humans; Inflammation; Ligands; Molecular Targeted Therapy; Receptors, Aryl Hydrocarbon; Signal Transduction
PubMed: 24905409
DOI: 10.3390/ijms150610116 -
Frontiers in Immunology 2022Cell death and dysregulated clearance of dead cells play essential roles in the induction of chronic inflammatory processes and autoimmune diseases. Granulomatosis with... (Review)
Review
Cell death and dysregulated clearance of dead cells play essential roles in the induction of chronic inflammatory processes and autoimmune diseases. Granulomatosis with polyangiitis (GPA), a neutrophil-driven autoimmune disorder, is characterized by necrotizing inflammation predominantly of the respiratory tract and an anti-neutrophil cytoplasmic autoantibody (ANCA)-associated systemic necrotizing vasculitis. Defective regulation of neutrophil homeostasis and cell death mechanisms have been demonstrated in GPA. Disturbed efferocytosis (., phagocytosis of apoptotic neutrophils by macrophages) as well as cell death-related release of damage-associated molecular patterns (DAMP) such as high mobility group box 1 (HMGB1) contribute to chronic non-resolving inflammation in GPA. DAMP have been shown to induce innate as well as adaptive cellular responses thereby creating a prerequisite for the development of pathogenic autoimmunity. In this review, we discuss factors contributing to as well as the impact of regulated cell death (RCD) accompanied by DAMP-release as early drivers of the granulomatous tissue inflammation and autoimmune responses in GPA.
Topics: Humans; Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Autoimmunity; HMGB1 Protein; Immunogenic Cell Death; Autoimmune Diseases; Leukocyte Disorders; Inflammation
PubMed: 36275673
DOI: 10.3389/fimmu.2022.1007092 -
Cancer Medicine Jun 2023Patients with certain autoimmune conditions are at a reduced risk of developing breast cancer compared to the general population. Despite this, little is known about...
BACKGROUND
Patients with certain autoimmune conditions are at a reduced risk of developing breast cancer compared to the general population. Despite this, little is known about outcomes in patients with breast cancer who have a concurrent autoimmune diagnosis.
METHODS
This study compared differences in outcomes between women with breast cancer who had or did not have an autoimmune diagnosis. The SEER-Medicare databases (2007-2014) were used to identify patients with breast cancer and diagnosis codes were used to identify those with an autoimmune disorder.
RESULTS
The studied autoimmune diseases had a prevalence of 27% among the 137,324 patients with breast cancer. Autoimmune disease was associated with significantly longer overall survival (OS) and significantly lower cancer-specific mortality (CSM) among stage IV breast cancer patients (p < 0.0001). After controlling for the effects of age, race, chronic kideny disease, chemotherapy, and radiation therapy autoimmune disease was still predictive of improved OS (HR: 1.45, 95% CI: 1.35-1.55, p < 0.0001) and CSM (HR: 1.40, 95% CI: 1.29-1.5, p < 0.0001). By contrast, in patients with stage I-III breast cancer, the presence of an autoimmune diagnosis was associated with a lower OS (p < 0.0001, p < 0.0001, and p = 0.026, respectively), compared to patients without autoimmune disease.
CONCLUSIONS
We found a higher prevalence of rheumatoid arthritis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus in patients with breast cancer compared to age matched cohorts in the general population. The presence of an autoimmune diagnosis was associated with a lower OS in stages I-III breast cancer and improved OS and CSM in patients with stage IV disease. These results suggest that anti-tumor immunity plays an important role in late stage breast cancer and could potentially be exploited to improve the effectiveness of immunotherapy.
Topics: Humans; Female; Aged; United States; Breast Neoplasms; Medicare; Autoimmune Diseases; SEER Program; Neoplasm Staging
PubMed: 37102221
DOI: 10.1002/cam4.5989 -
Cleveland Clinic Journal of Medicine Mar 2016Celiac disease is a multisystem autoimmune disorder that can cause symptoms involving the gastrointestinal tract and other organ systems such as the skin and bones. This... (Review)
Review
Celiac disease is a multisystem autoimmune disorder that can cause symptoms involving the gastrointestinal tract and other organ systems such as the skin and bones. This paper reviews the pathogenesis, diagnosis, and management of celiac disease and associated diseases.
Topics: Autoimmune Diseases; Celiac Disease; Disease Management; Humans
PubMed: 26974993
DOI: 10.3949/ccjm.83a.14158 -
Frontiers in Immunology 2019Over the past three decades, a considerable body of evidence has highlighted T cells as pivotal culprits in the pathogenesis of psoriasis. This includes the association... (Review)
Review
Over the past three decades, a considerable body of evidence has highlighted T cells as pivotal culprits in the pathogenesis of psoriasis. This includes the association of psoriasis with certain MHC (HLA) alleles, oligoclonal expansion of T cells in some cases, therapeutic response to T cell-directed immunomodulation, the onset of psoriasis following bone marrow transplantation, or induction of psoriasis-like inflammation by T cells in experimental animals. There is accumulating clinical and experimental evidence suggesting that both autoimmune and autoinflammatory mechanisms lie at the core of the disease. Indeed, some studies suggested antigenic functions of structural proteins, and complexes of self-DNA with cathelicidin (LL37) or melanocytic ADAMTSL5 have been proposed more recently as actual auto-antigens in some cases of psoriasis. These findings are accompanied by various immunoregulatory mechanisms, which we increasingly understand and which connect innate and adaptive immunity. Specific adaptive autoimmune responses, together with our current view of psoriasis as a systemic inflammatory disorder, raise the question of whether psoriasis may have connections to autoimmune or autoinflammatory disorders elsewhere in the body. While such associations have been suspected for many years, compelling mechanistic evidence in support of this notion is still scant. This review sets into context the current knowledge about innate and adaptive immunological processes in psoriasis and other autoimmune or autoinflammatory diseases.
Topics: Adaptive Immunity; Animals; Autoimmune Diseases; Autoimmunity; Disease Susceptibility; Humans; Immunity, Innate; Inflammation; Interleukin-17; Interleukin-23; Psoriasis; Skin
PubMed: 31402919
DOI: 10.3389/fimmu.2019.01764 -
Proceedings of the National Academy of... Oct 2020IL-17A is a therapeutic target in many autoimmune diseases. Most nonhematopoietic cells express IL-17A receptors and respond to extracellular IL-17A by inducing...
IL-17A is a therapeutic target in many autoimmune diseases. Most nonhematopoietic cells express IL-17A receptors and respond to extracellular IL-17A by inducing proinflammatory cytokines. The IL-17A signal transduction triggers two broad, TRAF6- and TRAF5-dependent, intracellular signaling pathways to produce representative cytokines (IL-6) and chemokines (CXCL-1), respectively. Our limited understanding of the cross-talk between these two branches has generated a crucial gap of knowledge, leading to therapeutics indiscriminately blocking IL-17A and global inhibition of its target genes. In previous work, we discovered an elevated expression of 14-3-3 proteins in inflammatory aortic disease, a rare human autoimmune disorder with increased levels of IL-17A. Here we report that 14-3-3ζ is essential for IL-17 signaling by differentially regulating the signal-induced IL-6 and CXCL-1. Using genetically manipulated human and mouse cells, and ex vivo and in vivo rat models, we uncovered a function of 14-3-3ζ. As a part of the molecular mechanism, we show that 14-3-3ζ interacts with several TRAF proteins; in particular, its interaction with TRAF5 and TRAF6 is increased in the presence of IL-17A. In contrast to TRAF6, we found TRAF5 to be an endogenous suppressor of IL-17A-induced IL-6 production, an effect countered by 14-3-3ζ. Furthermore, we observed that 14-3-3ζ interaction with TRAF proteins is required for the IL-17A-induced IL-6 levels. Together, our results show that 14-3-3ζ is an essential component of IL-17A signaling and IL-6 production, an effect that is suppressed by TRAF5. To the best of our knowledge, this report of the 14-3-3ζ-TRAF5 axis, which differentially regulates IL-17A-induced IL-6 and CXCL-1 production, is unique.
Topics: 14-3-3 Proteins; Animals; Autoimmune Diseases; Chemokine CXCL1; Chemokines; Cytokines; Gene Expression Regulation; Humans; Interleukin-17; Interleukin-6; Mice; Rats; Signal Transduction; TNF Receptor-Associated Factor 5; TNF Receptor-Associated Factor 6
PubMed: 32968020
DOI: 10.1073/pnas.2008214117 -
Neurogastroenterology and Motility Jul 2022Achalasia is a rare esophageal motility disorder of uncertain etiology. While past studies have indicated that autoimmune conditions and viral infections may be...
BACKGROUND
Achalasia is a rare esophageal motility disorder of uncertain etiology. While past studies have indicated that autoimmune conditions and viral infections may be associated with development of achalasia, these associations are yet to be examined in large, population-based studies.
METHODS
A matched case-control study was performed using administrative claim data from the IBM MarketScan Commercial Claims and Encounters Database between 2000 and 2019. A history of selected autoimmune conditions and viral infections was assessed using past medical claims. Multivariable conditional logistic regression was used to account for the matched nature of the study design and further control for confounding by demographic and clinical characteristics when reporting adjusted odds ratios (aORs).
KEY RESULTS
Among 6769 cases and 27,076 controls, presence of any of the autoimmune conditions studied was associated with increased odds of achalasia (aOR = 1.26, 95% CI: 1.11, 1.42). Scleroderma or systemic sclerosis (aOR = 8.13, 95% CI: 3.34, 19.80) and Addison's disease (aOR = 3.83, 95% CI: 1.83, 8.04) had the strongest associations with achalasia. Presence of any of the viral infections studied was also associated with an increased risk of achalasia (aOR = 1.58, 95% CI: 1.23, 2.01). Varicella zoster virus (aOR = 3.84, 95% CI: 1.94, 7.62) and human papillomavirus (aOR = 1.77, 95% CI: 1.15, 2.73) both had strong relationships with achalasia.
CONCLUSIONS AND INFERENCES
These findings suggest that achalasia may have autoimmune and viral components contributing to its etiology. Future mechanistic studies could target specific diseases and agents highlighted by this research.
Topics: Autoimmune Diseases; Case-Control Studies; Esophageal Achalasia; Esophageal Motility Disorders; Humans; Risk Factors; Scleroderma, Systemic; Virus Diseases
PubMed: 34957646
DOI: 10.1111/nmo.14312