scholarly journals Polymorphism in BACH2 gene is a marker of polyglandular autoimmunity

Endocrine ◽  
2021 ◽  
Author(s):  
Marta Fichna ◽  
Magdalena Żurawek ◽  
Bartosz Słomiński ◽  
Marta Sumińska ◽  
Agata Czarnywojtek ◽  
...  
Keyword(s):  
Immune Cell ◽  
Premature Menopause ◽  
Complex Disorders ◽  
Increased Risk ◽  
Organ Specific ◽  
Autoimmune Conditions ◽  
Cell Balance ◽  
Type 3 ◽  
Polyglandular Autoimmunity

Abstract Purpose Genetically predisposed individuals may develop several autoimmune diseases—autoimmune polyendocrine syndromes (APS). APS types 2–4, are complex disorders, which combine various organ-specific autoimmune conditions. Recent reports support the considerable role of the BACH2 gene in immune cell differentiation and shifting the T-cell balance towards regulatory T-cells. BACH2 polymorphisms are associated with autoimmune disorders, including Addison’s disease (AD), Graves’ disease (GD), and probably type 1 diabetes (T1D). Our study was aimed to investigate the BACH2 variant, rs3757247, in endocrine autoimmunity in the Polish population. Methods The analysis comprised 346 individuals with APS, 387 with T1D only, and 568 controls. Genotyping was performed using TaqMan chemistry. Results APS type 2 was found in 219 individuals, type 3 in 102, and type 4 in 25 subjects. Overall, AD was diagnosed in 244 subjects, Hashimoto’s thyroiditis—in 238, T1D—in 127, GD—in 58, vitiligo and chronic gastritis each in 40 patients, celiac disease—in 28, premature menopause in 18, and alopecia in 4 patients. Minor T allele at rs3757247 was found in 56.4% APS vs. 44.1% control alleles (OR 1.59; 95%CI: 1.30–1.95, p < 0.0001). The distribution of genotypes revealed excess TT homozygotes in the APS cohort (33.2 vs. 20.1% in controls, p < 0.0001). The frequencies of rs3757247 alleles and genotypes in T1D patients did not present significant differences vs. controls (p-values > 0.05). Conclusions These results provide evidence of the association between BACH2 polymorphism and polyglandular autoimmunity. Since carriers of rs3757247 display increased risk for additional autoimmune conditions, this variant could identify individuals prone to develop APS.

scholarly journals Cardiac Tissue Factor Regulates Inflammation, Hypertrophy and Heart Failure in Mouse Model of Type 1 Diabetes

2021 ◽  
Author(s):  
Dasan Mary Cibi ◽  
Reddemma Sandireddy ◽  
Hanumakumar Bogireddy ◽  
Nicole Tee ◽  
Siti Aishah Binte Abdul Ghani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Tissue Factor ◽  
Cardiac Tissue ◽  
Immune Cell ◽  
Preserved Ejection Fraction ◽  
Cardiac Inflammation ◽  
Protein Levels ◽  
Increased Risk

Diabetes patients have an increased risk of heart failure (HF). Diabetes is highly prevalent in HF with preserved ejection fraction (HFpEF), which is on the rise worldwide. The role of diabetes in HF is less established and available treatments of HF are not effective in HFpEF patients. Tissue factor (TF), a transmembrane receptor, plays an important role in immune-cell inflammation and atherothrombosis in diabetes. However, its role in diabetes-induced cardiac inflammation, hypertrophy, and HF has not been studied. Here, we have utilized Wildtype (WT), heterozygous, and Low-TF (with 1% human TF) mice to determine TF’s role in <i>Type1 diabetes</i>-induced HF. We found significant upregulation of cardiac TF mRNA and protein levels in diabetic WT hearts compared to non-diabetic controls. WT diabetic hearts also exhibited increased inflammation and cardiac hypertrophy versus controls. However, these changes in cardiac inflammation and hypertrophy were not found in diabetic Low-TF mice compared to their non-diabetic controls. TF deficiency was also associated with improved cardiac function parameters suggestive of HFpEF, which was evident in diabetic WT mice. The TF regulation of inflammation and cardiac remodeling was further dependent on downstream ERK1/2 and STAT3 pathways. In summary, our study demonstrated an important role of TF in regulating diabetes-induced inflammation, hypertrophy, and remodeling of the heart leading to HF with preserved ejection fraction.

scholarly journals Risk-Reducing Bilateral Salpingo-Oophorectomy for Ovarian Cancer: A Review and Clinical Guide for Hereditary Predisposition Genes

2021 ◽  
Author(s):  
Ying L. Liu ◽  
Kelsey Breen ◽  
Amanda Catchings ◽  
Megha Ranganathan ◽  
Alicia Latham ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Individual Risk ◽  
Premature Menopause ◽  
National Guidelines ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
New Guidelines ◽  
Risk Reducing

Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/ 2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/ D where the risk of OC is elevated beyond our threshold for RRSO. In PALB1, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points.

scholarly journals Cardiac Tissue Factor Regulates Inflammation, Hypertrophy and Heart Failure in Mouse Model of Type 1 Diabetes

2021 ◽  
Author(s):  
Dasan Mary Cibi ◽  
Reddemma Sandireddy ◽  
Hanumakumar Bogireddy ◽  
Nicole Tee ◽  
Siti Aishah Binte Abdul Ghani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Tissue Factor ◽  
Cardiac Tissue ◽  
Immune Cell ◽  
Preserved Ejection Fraction ◽  
Cardiac Inflammation ◽  
Protein Levels ◽  
Increased Risk

Diabetes patients have an increased risk of heart failure (HF). Diabetes is highly prevalent in HF with preserved ejection fraction (HFpEF), which is on the rise worldwide. The role of diabetes in HF is less established and available treatments of HF are not effective in HFpEF patients. Tissue factor (TF), a transmembrane receptor, plays an important role in immune-cell inflammation and atherothrombosis in diabetes. However, its role in diabetes-induced cardiac inflammation, hypertrophy, and HF has not been studied. Here, we have utilized Wildtype (WT), heterozygous, and Low-TF (with 1% human TF) mice to determine TF’s role in <i>Type1 diabetes</i>-induced HF. We found significant upregulation of cardiac TF mRNA and protein levels in diabetic WT hearts compared to non-diabetic controls. WT diabetic hearts also exhibited increased inflammation and cardiac hypertrophy versus controls. However, these changes in cardiac inflammation and hypertrophy were not found in diabetic Low-TF mice compared to their non-diabetic controls. TF deficiency was also associated with improved cardiac function parameters suggestive of HFpEF, which was evident in diabetic WT mice. The TF regulation of inflammation and cardiac remodeling was further dependent on downstream ERK1/2 and STAT3 pathways. In summary, our study demonstrated an important role of TF in regulating diabetes-induced inflammation, hypertrophy, and remodeling of the heart leading to HF with preserved ejection fraction.

scholarly journals Type 3 muscarinic receptors contribute to intestinal mucosal homeostasis and clearance of Nippostrongylus brasiliensis through induction of TH2 cytokines

2016 ◽  
Vol 311 (1) ◽  
pp. G130-G141 ◽  
Author(s):  
Leon P. McLean ◽  
Allen Smith ◽  
Lumei Cheung ◽  
Joseph F. Urban ◽  
Rex Sun ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Host Defense ◽  
Cell Function ◽  
Immune Cell ◽  
Nippostrongylus Brasiliensis ◽  
Epithelial Secretion ◽  
Mucosal Homeostasis ◽  
Small Intestinal ◽  
Type 3

Despite increased appreciation for the role of nicotinic receptors in the modulation of and response to inflammation, the contribution of muscarinic receptors to mucosal homeostasis, clearance of enteric pathogens, and modulation of immune cell function remains relatively undefined. Uninfected and Nippostrongylus brasiliensis-infected wild-type and type 3 muscarinic receptor (M3R)-deficient ( Chrm3 −/−) mice were studied to determine the contribution of M3R to mucosal homeostasis as well as host defense against the TH2-eliciting enteric nematode N. brasiliensis. Intestinal permeability and expression of TH1/TH17 cytokines were increased in uninfected Chrm3 −/− small intestine. Notably, in Chrm3 −/− mice infected with N. brasiliensis, small intestinal upregulation of TH2 cytokines was attenuated and nematode clearance was delayed. In Chrm3 −/− mice, TH2-dependent changes in small intestinal function including smooth muscle hypercontractility, increased epithelial permeability, decreased epithelial secretion and absorption, and goblet cell expansion were absent despite N. brasiliensis infection. These findings identify an important role for M3R in host defense and clearance of N. brasiliensis, and support the expanding role of cholinergic muscarinic receptors in maintaining mucosal homeostasis.

scholarly journals Influence of PTPN22 Allotypes on Innate and Adaptive Immune Function in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Lucas H. Armitage ◽  
Mark A. Wallet ◽  
Clayton E. Mathews
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Tyrosine Phosphatase ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
Increased Risk ◽  
Core Function ◽  
Health And Disease

Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) regulates a panoply of leukocyte signaling pathways. A single nucleotide polymorphism (SNP) in PTPN22, rs2476601, is associated with increased risk of Type 1 Diabetes (T1D) and other autoimmune diseases. Over the past decade PTPN22 has been studied intensely in T cell receptor (TCR) and B cell receptor (BCR) signaling. However, the effect of the minor allele on PTPN22 function in TCR signaling is controversial with some reports concluding it has enhanced function and blunts TCR signaling and others reporting it has reduced function and increases TCR signaling. More recently, the core function of PTPN22 as well as functional derangements imparted by the autoimmunity-associated variant allele of PTPN22 have been examined in monocytes, macrophages, dendritic cells, and neutrophils. In this review we will discuss the known functions of PTPN22 in human cells, and we will elaborate on how autoimmunity-associated variants influence these functions across the panoply of immune cells that express PTPN22. Further, we consider currently unresolved questions that require clarification on the role of PTPN22 in immune cell function.

Vitamin A: dietologist’s position

2020 ◽  
pp. 49-57
Author(s):  
S. V. Orlova ◽  
E. A. Nikitina ◽  
L. I. Karushina ◽  
Yu. A. Pigaryova ◽  
O. E. Pronina
Keyword(s):  
Immune Response ◽  
Urinary Tract ◽  
Gastrointestinal Tract ◽  
Vitamin A ◽  
Developed Countries ◽  
Therapeutic Practice ◽  
The Past ◽  
Increased Risk ◽  
Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

Myocardial Noncompaction

2018 ◽  
Vol 69 (8) ◽  
pp. 2209-2212
Author(s):  
Alexandru Radu Mihailovici ◽  
Vlad Padureanu ◽  
Carmen Valeria Albu ◽  
Venera Cristina Dinescu ◽  
Mihai Cristian Pirlog ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Specific Treatment ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Genetic Transmission ◽  
Asymptomatic Patients ◽  
Increased Risk ◽  
Patients With Heart Failure

Left ventricular noncompaction is a primary cardiomyopathy with genetic transmission in the vast majority of autosomal dominant cases. It is characterized by the presence of excessive myocardial trabecularities that generally affect the left ventricle. In diagnosing this condition, echocardiography is the gold standard, although this method involves an increased risk of overdiagnosis and underdiagnosis. There are also uncertain cases where echocardiography is inconclusive, a multimodal approach is needed, correlating echocardiographic results with those obtained by magnetic resonance imaging. The clinical picture may range from asymptomatic patients to patients with heart failure, supraventricular or ventricular arrhythmias, thromboembolic events and even sudden cardiac death. There is no specific treatment of left ventricular noncompaction, but the treatment is aimed at preventing and treating the complications of the disease. We will present the case of a young patient with left ventricular noncompactioncardiomyopathy and highlight the essential role of transthoracic echocardiography in diagnosing this rare heart disease.

Semi-Quantitative Ultrasonographic Evaluation of NAFLD

2020 ◽  
Vol 26 (32) ◽  
pp. 3915-3927 ◽  
Author(s):  
Stefano Ballestri ◽  
Claudio Tana ◽  
Maria Di Girolamo ◽  
Maria Cristina Fontana ◽  
Mariano Capitelli ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Imaging Techniques ◽  
Metabolic Complications ◽  
Nonalcoholic Fatty Liver ◽  
Non Invasive ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Progressive Liver Disease

: Nonalcoholic fatty liver disease (NAFLD) embraces histopathological entities ranging from the relatively benign simple steatosis to the progressive form nonalcoholic steatohepatitis (NASH), which is associated with fibrosis and an increased risk of progression to cirrhosis and hepatocellular carcinoma. NAFLD is the most common liver disease and is associated with extrahepatic comorbidities including a major cardiovascular disease burden. : The non-invasive diagnosis of NAFLD and the identification of subjects at risk of progressive liver disease and cardio-metabolic complications are key in implementing personalized treatment schedules and follow-up strategies. : In this review, we highlight the potential role of ultrasound semiquantitative scores for detecting and assessing steatosis severity, progression of NAFLD, and cardio-metabolic risk. : Ultrasonographic scores of fatty liver severity act as sensors of cardio-metabolic health and may assist in selecting patients to submit to second-line non-invasive imaging techniques and/or liver biopsy.

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

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