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https://www.readbyqxmd.com/read/29040339/protein-tyrosine-phosphatase-ptpn22-is-dispensable-for-dendritic-cell-antigen-processing-and-promotion-of-t-cell-activation-by-dendritic-cells
#1
Fiona Clarke, Christine K Jordan, Enrique Gutiérrez-Martinez, Jack A Bibby, Cristina Sanchez-Blanco, Georgina H Cornish, Xuezhi Dai, David J Rawlings, Rose Zamoyska, Pierre Guermonprez, Andrew P Cope, Harriet A Purvis
The PTPN22R620W single nucleotide polymorphism increases the risk of developing multiple autoimmune diseases including type 1 diabetes, rheumatoid arthritis and lupus. PTPN22 is highly expressed in antigen presenting cells (APCs) where the expression of the murine disease associated variant orthologue (Ptpn22R619W) is reported to dysregulate pattern recognition receptor signalling in dendritic cells (DCs) and promote T-cell proliferation. Because T-cell activation is dependent on DC antigen uptake, degradation and presentation, we analysed the efficiency of these functions in splenic and GM-CSF bone marrow derived DC from wild type (WT), Ptpn22-/- or Ptpn22R619W mutant mice...
2017: PloS One
https://www.readbyqxmd.com/read/29040050/latent-autoimmune-diabetes-in-adults-in-north-indian-region-assessment-of-%C3%AE-cell-function-metabolic-and-immunological-features
#2
Alok Kumar, Alberto de Leiva
BACKGROUND: We undertook a study to assess β-cell function and metabolic and immunological features of patients with latent autoimmune diabetes in adults (LADA) and assess heterogeneity within LADA based on low and high glutamic acid decarboxylase autoantibodies (GADA) titers. METHODS: A total of 139 patients with adult-onset diabetes were examined cross-sectionally in the National capital region of Northern India. Medical history of all subjects was reviewed with the aim of collecting clinical data...
October 17, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/29034636/-high-dose-heat-shock-protein-gp96-immunization-prevents-type-1-diabetes-via-inducing-regulatory-t-cells
#3
Mi Chen, Xinghui Li, Huaguo Zheng, Songdong Meng
Type 1 diabetes (T1D), the most prevalent human autoimmune disease, occurs in genetically susceptible individuals. Regulatory T cells (Tregs) are defective in T1D setting. Therefore, efforts to repair or restore Tregs in T1D may prevent or reverse this autoimmune disease. Here, we studied the potential role of rgp96 in preventing T1D, using non-obese diabetic (NOD) mice as an animal model. High-dose rgp96 immunization elicited efficient protection of mice against T1D, as evidenced by stable blood glucose, decreased disease incidence...
December 25, 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/29034607/complete-loss-of-insulin-secretion-capacity-in-type-1a-diabetic-patients-during-long-term-follow-up
#4
Sae Uno, Akihisa Imagawa, Junji Kozawa, Kenji Fukui, Hiromi Iwahashi, Iichiro Shimomura
AIM/INTRODUCTION: The patients with type 1 diabetes are classified into three subtypes: acute-onset, fulminant, and slowly progressive in Japan. Acute-onset type 1 diabetes would be equivalent to type 1A diabetes, the typical type 1 diabetes in Western countries. The insulin secretion capacity in Japanese subjects with long-standing type 1A diabetes is unclear. The aim of this study is to clarify the course of endogenous insulin secretion during long-term follow-up and factors associated with residual insulin secretion in patients with acute-onset type 1 diabetes (autoimmune)...
October 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29033948/unique-features-of-pancreatic-resident-regulatory-t-cells-in-autoimmune-type-1-diabetes
#5
REVIEW
Jingli Lu, Chaoqi Zhang, Lifeng Li, Wenhua Xue, Chengliang Zhang, Xiaojian Zhang
Recent progress in regulatory T cells (Tregs) biology emphasizes the importance of understanding tissue-resident Tregs in response to tissue-specific environment. Now, emerging evidence suggests that pancreatic-resident forkhead box P3(+) Tregs have distinguishable effects on the suppression of over-exuberant immune responses in autoimmune type 1 diabetes (T1D). Thus, there is growing interest in elucidating the role of pancreatic-resident Tregs that function and evolve in the local environment. In this review, we discuss the phenotype and function of Tregs residing in pancreatic tissues and pancreatic lymph nodes, with emphasis on the unique subpopulations of Tregs that control the disease progression in the context of T1D...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033938/early-life-nutritional-factors-and-mucosal-immunity-in-the-development-of-autoimmune-diabetes
#6
REVIEW
Ling Xiao, Belinda Van't Land, Wouter R P H van de Worp, Bernd Stahl, Gert Folkerts, Johan Garssen
Type 1 diabetes (T1D) is an immune-mediated disease with a strong genetic basis but might be influenced by non-genetic factors such as microbiome development that "programs" the immune system during early life as well. Factors influencing pathogenesis, including a leaky intestinal mucosal barrier, an aberrant gut microbiota composition, and altered immune responsiveness, offer potential targets for prevention and/or treatment of T1D through nutritional or pharmacologic means. In this review, nutritional approaches during early life in order to protect against T1D development have been discussed...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033899/environmental-factors-contribute-to-%C3%AE-cell-endoplasmic-reticulum-stress-and-neo-antigen-formation-in-type-1-diabetes
#7
Meghan L Marré, Jon D Piganelli
Type 1 diabetes (T1D) is an autoimmune disease in which immune-mediated targeting and destruction of insulin-producing pancreatic islet β cells leads to chronic hyperglycemia. There are many β cell proteins that are targeted by autoreactive T cells in their native state. However, recent studies have demonstrated that many β cell proteins are recognized as neo-antigens following posttranslational modification (PTM). Although modified neo-antigens are well-established targets of pathology in other autoimmune diseases, the effects of neo-antigens in T1D progression and the mechanisms by which they are generated are not well understood...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29033611/stable-ischemic-heart-disease-in-women-current-perspectives
#8
REVIEW
Fatima Samad, Anushree Agarwal, Zainab Samad
Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm, plaque erosion and spontaneous coronary artery dissection. Angina is the most common presentation of stable ischemic heart disease (SIHD) in women. Risk factors for SIHD include traditional risks such as older age, obesity (body mass index [BMI] >25 kg/m(2)), smoking, hypertension, dyslipidemia, cerebrovascular and peripheral vascular disease, sedentary lifestyle, family history of premature coronary artery disease, metabolic syndrome and diabetes mellitus, and nontraditional risk factors, such as gestational diabetes, insulin resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre-eclampsia, eclampsia, menopause, mental stress and autoimmune diseases...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/29031410/harnessing-gut-microbes-for-mental-health-getting-from-here-to-there
#9
REVIEW
Annadora J Bruce-Keller, J Michael Salbaum, Hans-Rudolf Berthoud
There has been an explosion of interest in the study of microorganisms inhabiting the gastrointestinal tract (gut microbiota) and their impact on host health and physiology. Accumulating data suggest that altered communication between gut microbiota and host systems could participate in disorders such as obesity, diabetes mellitus, and autoimmune disorders as well as neuropsychiatric disorders, including autism, anxiety, and major depressive disorders. The conceptual development of the microbiome-gut-brain axis has facilitated understanding of the complex and bidirectional networks between gastrointestinal microbiota and their host, highlighting potential mechanisms through which this environment influences central nervous system physiology...
August 30, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29030662/oral-histone-deacetylase-inhibitor-synergises-with-t-cell-targeted-immunotherapy-to-preserve-beta-cell-metabolic-function-and-induce-stable-remission-of-new-onset-autoimmune-diabetes-in-nod-mice
#10
Alix Besançon, Tania Goncalves, Fabrice Valette, Mattias S Dahllöf, Thomas Mandrup-Poulsen, Lucienne Chatenoud, Sylvaine You
AIM/HYPOTHESIS: Combination therapy targeting the major actors involved in the immune-mediated destruction of pancreatic beta cells appears to be an indispensable approach to treat type 1 diabetes effectively. We hypothesised that the combination of an orally active pan-histone deacetylase inhibitor (HDACi: givinostat) with subtherapeutic doses of CD3 antibodies may provide ideal synergy to treat ongoing autoimmunity. METHODS: NOD mice transgenic for the human CD3ε (also known as CD3E) chain (NOD-huCD3ε) were treated for recent-onset diabetes with oral givinostat, subtherapeutic doses of humanised CD3 antibodies (otelixizumab, 50 μg/day, 5 days, i...
October 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/29026609/ketosis-prone-diabetes-and-sle-co-presenting-in-an-african-lady-with-previous-gestational-diabetes
#11
S Hussain, S Keat, S V Gelding
We describe the case of an African woman who was diagnosed with ketosis-prone diabetes with diabetes-associated autoantibodies, after being admitted for diabetic ketoacidosis (DKA) precipitated by her first presentation of systemic lupus erythematosus (SLE). She had a seven-year history of recurrent gestational diabetes (GDM) not requiring insulin therapy, with return to normoglycaemia after each pregnancy. This might have suggested that she had now developed type 2 diabetes (T2D). However, the diagnosis of SLE prompted testing for an autoimmune aetiology for the diabetes, and she was found to have a very high titre of GAD antibodies...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29025893/disease-specific-biases-in-alternative-splicing-and-tissue-specific-dysregulation-revealed-by-multitissue-profiling-of-lymphocyte-gene-expression-in-type-1-diabetes
#12
Jeremy R B Newman, Ana Conesa, Matthew Mika, Felicia N New, Suna Onengut-Gumuscu, Mark A Atkinson, Stephen S Rich, Lauren M McIntyre, Patrick Concannon
Genome-wide association studies (GWAS) have identified multiple, shared allelic associations with many autoimmune diseases. However, the pathogenic contributions of variants residing in risk loci remain unresolved. The location of the majority of shared disease-associated variants in noncoding regions suggests they contribute to risk of autoimmunity through effects on gene expression in the immune system. In the current study, we test this hypothesis by applying RNA sequencing to CD4(+), CD8(+), and CD19(+) lymphocyte populations isolated from 81 subjects with type 1 diabetes (T1D)...
October 12, 2017: Genome Research
https://www.readbyqxmd.com/read/29025879/tcf7l2-genetic-variants-contribute-to-phenotypic-heterogeneity-of-type-1-diabetes
#13
Maria J Redondo, Susan Geyer, Andrea K Steck, Jay Sosenko, Mark Anderson, Peter Antinozzi, Aaron Michels, John Wentworth, Ping Xu, Alberto Pugliese
OBJECTIVE: The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 (TCF7L2) single nucleotide polymorphisms (SNP) with immunologic and metabolic characteristics at type 1 diabetes diagnosis. RESEARCH DESIGN AND METHODS: We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data (n = 810; median age 13...
October 12, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29025857/endocrine-side-effects-of-cancer-immunotherapy
#14
Priscilla Cukier, Fernando C Santini, Mariana Scaranti, Ana O Hoff
Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine related irAEs...
October 12, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29023853/antibiotics-gut-microbiome-and-obesity
#15
Karen S W Leong, José G B Derraik, Paul L Hofman, Wayne S Cutfield
Antibiotics have been hailed by many as 'miracle drugs' that have been effectively treating infectious diseases for over a century, leading to a marked reduction in morbidity and mortality. However, with the increasing use of antibiotics, we are now faced not only with the increasing threat of antibiotic resistance, but also with a rising concern about potential long-term effects of antibiotics on human health, including the development of obesity. The obesity pandemic continues to increase, a problem that affects both adults and children alike...
October 12, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/29021891/a-good-sugar-d-mannose-suppresses-autoimmune-diabetes
#16
Yun-Bo Shi, Deling Yin
It is well known that too much sugar uptake causes many health problems, including diabetes and obesity (Lustig et al. in Nature 482:27-29, 2012). However, a team of researchers led by Dr. Wanjun Chen of the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), USA, have recently shown that d-mannose, a naturally occurring C-2 epimer of glucose is likely beneficial to human health. Their studies have revealed that supraphysiological levels of d-mannose that are safely achievable via drinking-water supplementation can be preventive and therapeutic to experimental autoimmune diabetes and asthmatic lung inflammation (Zhang et al...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29021840/vaccination-and-autoimmune-diseases-is-prevention-of-adverse-health-effects-on-the-horizon
#17
REVIEW
Maria Vadalà, Dimitri Poddighe, Carmen Laurino, Beniamino Palmieri
Autoimmune diseases, including multiple sclerosis and type 1 diabetes mellitus, affect about 5% of the worldwide population. In the last decade, reports have accumulated on various autoimmune disorders, such as idiopathic thrombocytopenia purpura, myopericarditis, primary ovarian failure, and systemic lupus erythematosus (SLE), following vaccination. In this review, we discuss the possible underlying mechanisms of autoimmune reactions following vaccinations and review cases of autoimmune diseases that have been correlated with vaccination...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/29018826/high-prevalence-of-autoimmune-diabetes-and-poor-glycaemic-control-among-adults-in-madagascar-a-brief-report-from-a-humanitarian-health-campaign-in-ambanja
#18
Ernesto Maddaloni, Giovanlorenzo Pastore, Marco Giuseppe Del Buono, Aldostefano Porcari, Mario Fittipaldi, Francesco Garilli, Claudio Tiberti, Silvia Angeletti, Paolo Pozzilli, Giovanni Mottini, Nicola Napoli
Madagascar is a geographically isolated country considered a biodiversity hotspot with unique genomics. Both the low-income and the geographical isolation represent risk factors for the development of diabetes. During a humanitarian health campaign conducted in Ambanja, a rural city in the northern part of Madagascar, we identified 42 adult subjects with diabetes and compared their features to 24 randomly enrolled healthy controls. 42.9% (n = 18) of diabetic subjects showed HbA1c values ≥ 9.0%. Unexpectedly, waist circumference and BMI were similar in people with diabetes and controls...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29018409/innate-viral-receptor-signaling-determines-type-1-diabetes-onset
#19
REVIEW
Zachary J Morse, Marc S Horwitz
Heritable susceptibility of the autoimmune disorder, type 1 diabetes (T1D), only partially equates for the incidence of the disease. Significant evidence attributes several environmental stressors, such as vitamin D deficiency, gut microbiome, dietary antigens, and most notably virus infections in triggering the onset of T1D in these genetically susceptible individuals. Extensive epidemiological and clinical studies have provided credibility to this causal relationship. Infection by the enterovirus, coxsackievirus B, has been closely associated with onset of T1D and is considered a significant etiological agent for disease induction...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29018046/co-occurrence-of-type-1-diabetes-and-celiac-disease-autoimmunity
#20
William Hagopian, Hye-Seung Lee, Edwin Liu, Marian Rewers, Jin-Xiong She, Anette-G Ziegler, Åke Lernmark, Jorma Toppari, Stephen S Rich, Jeffrey P Krischer, Henry Erlich, Beena Akolkar, Daniel Agardh
BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors. METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed...
October 10, 2017: Pediatrics
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