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Autoimmune pancreatitis

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https://www.readbyqxmd.com/read/28929796/a-coordinated-control-strategy-for-insulin-and-glucagon-delivery-in-type-1-diabetes
#1
Pau Herrero, Jorge Bondia, Nick Oliver, Pantelis Georgiou
Type 1 diabetes is an autoimmune condition characterised by a pancreatic insulin secretion deficit, resulting in high blood glucose concentrations, which can lead to micro- and macrovascular complications. Type 1 diabetes also leads to impaired glucagon production by the pancreatic α-cells, which acts as a counter-regulatory hormone to insulin. A closed-loop system for automatic insulin and glucagon delivery, also referred to as an artificial pancreas, has the potential to reduce the self-management burden of type 1 diabetes and reduce the risk of hypo- and hyperglycemia...
September 20, 2017: Computer Methods in Biomechanics and Biomedical Engineering
https://www.readbyqxmd.com/read/28925365/generation-of-an-induced-pluripotent-stem-cell-ipsc-line-from-a-patient-with-maturity-onset-diabetes-of-the-young-type-13-mody13-with-a-the-potassium-inwardly-rectifying-channel-subfamily-j-member-11-kcnj11-mutation
#2
Frank Griscelli, Olivier Feraud, Tony Ernault, Noufissa Oudrihri, Ali G Turhan, Amélie Bonnefond, Philippe Froguel, Annelise Bennaceur-Griscelli
Heterozygous activating mutation (p.Glu227Lys) in KCNJ11 leads to maturity-onset diabetes of the young (MODY) type 13, that is a subtype of dominant inherited young-onset non-autoimmune diabetes due to a primary defect in pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs) from a patient with KCNJ11(p.Glu227Lys) mutation who developed MODY at 13years old. KCNJ11(p.Glu227Lys)-mutated cells that were reprogrammed by non-integrative viral transduction had normal karyotype, harboured the KCNJ11(p...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28921377/basophils-activated-via-tlr-signaling-may-contribute-to-pathophysiology-of-type-1-autoimmune-pancreatitis
#3
Masato Yanagawa, Kazushige Uchida, Yugo Ando, Takashi Tomiyama, Takashi Yamaguchi, Tsukasa Ikeura, Toshiro Fukui, Akiyoshi Nishio, Yoshiko Uemura, Takayuki Miyara, Hiroyuki Okamoto, Souhei Satoi, Kazuichi Okazaki
BACKGROUND: Pathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. In this study, we investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP. METHODS: By using immunohistochemistry, we investigated basophils in pancreatic tissue from 13 patients with type 1 AIP and examined expression of toll-like receptors (TLRs) by these cells...
September 18, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28918803/the-role-of-endoscopic-ultrasound-in-the-diagnosis-of-autoimmune-pancreatitis
#4
REVIEW
Larissa L Fujii-Lau, Michael J Levy
Autoimmune pancreatitis (AIP) is increasingly being recognized due to improved understanding of the disease and its criteria for diagnosis. The classic type 1 AIP can be diagnosed on clinical data, but type 2 AIP requires histologic confirmation. Current criteria incorporate cross-sectional imaging and endoscopic retrograde cholangiopancreatography in the diagnosis of AIP. However, endoscopic ultrasound (EUS) will likely have an increasing role in the diagnosis through its characteristic imaging, image-enhancing techniques, and its ability to acquire tissue through either fine needle aspiration or biopsy...
October 2017: Gastrointestinal Endoscopy Clinics of North America
https://www.readbyqxmd.com/read/28916403/a-case-of-severe-acquired-hypertriglyceridemia-in-a-7-year-old-girl
#5
Jessica S Lilley, MacRae F Linton, Jennifer C Kelley, T Brent Graham, Sergio Fazio, Hagai Tavori
We report a case of severe type I hyperlipoproteinemia caused by autoimmunity against lipoprotein lipase (LPL) in the context of presymptomatic Sjögren's syndrome. A 7-year-old mixed race (Caucasian/African American) girl was admitted to the intensive care unit at Vanderbilt Children's Hospital with acute pancreatitis and shock. She was previously healthy aside from asthma and history of Hashimoto's thyroiditis. Admission triglycerides (TGs) were 2191 mg/dL but returned to normal during the hospital stay and in the absence of food intake...
August 12, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28905689/igg4-related-cholangiopathy-and-its-mimickers-a-case-report-and-review-highlighting-the-importance-of-early-diagnosis
#6
Kyle Geary, Cemal Yazici, Anita Seibold, Grace Guzman
Immunoglobulin (Ig) G4 (IgG4)-related disease is a recently described clinical entity that can involve multiple organs. It is an autoimmune disorder characterized by a dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. A key distinguishing factor is its dramatic response to steroid therapy. Although best described in cases of autoimmune pancreatitis, IgG4-related disease has also been implicated in patients with cholangitis and is now commonly referred to as IgG4-related cholangiopathy...
September 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28889199/oral-delivery-of-staphylococcal-nuclease-by-lactococcus-lactis-prevents-type-1-diabetes-mellitus-in-nod-mice
#7
Junchao Lang, Xiaoke Wang, Kunfeng Liu, Dongmei He, Pancong Niu, Rongyue Cao, Liang Jin, Jie Wu
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the self-destruction of insulin-producing β cells. Recently, studies have revealed that neutrophils contribute to the early pathological injury to the pancreas, predominantly via the formation of neutrophil extracellular traps (NETs). To determine whether early intervention targeting NETs with staphylococcal nuclease (SNase) can delay the onset of T1DM, non-obese diabetic (NOD) mice were orally administered recombinant Lactococcus lactis (L...
September 9, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28880010/chronic-pancreatitis
#8
REVIEW
Jorg Kleeff, David C Whitcomb, Tooru Shimosegawa, Irene Esposito, Markus M Lerch, Thomas Gress, Julia Mayerle, Asbjørn Mohr Drewes, Vinciane Rebours, Fatih Akisik, J Enrique Domínguez Muñoz, John P Neoptolemos
Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood...
September 7, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28878738/overlooked-mechanisms-in-type-1-diabetes-etiology-how-unique-costimulatory-molecules-contribute-to-diabetogenesis
#9
REVIEW
David H Wagner
Type 1 Diabetes (T1D) develops when immune cells invade the pancreatic islets resulting in loss of insulin production in beta cells. T cells have been proven to be central players in that process. What is surprising, however, is that classic mechanisms of tolerance cannot explain diabetogenesis; alternate mechanisms must now be considered. T cell receptor (TCR) revision is the process whereby T cells in the periphery alter TCR expression, outside the safety-net of thymic selection pressures. This process results in an expanded T cell repertoire, capable of responding to a universe of pathogens, but limitations are that increased risk for autoimmune disease development occurs...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28878669/picrorhiza-kurroa-enhances-%C3%AE-cell-mass-proliferation-and-insulin-secretion-in-streptozotocin-evoked-%C3%AE-cell-damage-in-rats
#10
Shiv Kumar, Vikram Patial, Sourabh Soni, Supriya Sharma, Kunal Pratap, Dinesh Kumar, Yogendra Padwad
Autoimmune destruction of insulin producing pancreatic β-cells leads to insulin insufficiency and hyperglycemia in type 1 diabetes mellitus. Regeneration of β-cells is one of the proposed treatment for type 1 diabetes and insulin insufficiency. Picrorhiza kurroa is a medicinal herb and is traditionally being used for the treatment of various diseases. Previous studies reported the hypoglycemic potential of P. kurroa. However, its potential role in β-cell induction in insulin secretion have not been fully investigated...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28877460/persistence-of-pancreatic-insulin-mrna-expression-and-proinsulin-protein-in-type-1-diabetes-pancreata
#11
Clive Wasserfall, Harry S Nick, Martha Campbell-Thompson, Dawn Beachy, Leena Haataja, Irina Kusmartseva, Amanda Posgai, Maria Beery, Christopher Rhodes, Ezio Bonifacio, Peter Arvan, Mark Atkinson
The canonical notion that type 1 diabetes (T1D) results following a complete destruction of β cells has recently been questioned as small amounts of C-peptide are detectable in patients with long-standing disease. We analyzed protein and gene expression levels for proinsulin, insulin, C-peptide, and islet amyloid polypeptide within pancreatic tissues from T1D, autoantibody positive (Ab+), and control organs. Insulin and C-peptide levels were low to undetectable in extracts from the T1D cohort; however, proinsulin and INS mRNA were detected in the majority of T1D pancreata...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28877242/comparative-quantitative-proteomic-analysis-of-disease-stratified-laser-captured-microdissected-human-islets-identifies-proteins-and-pathways-potentially-related-to-type-1-diabetes
#12
Julius O Nyalwidhe, Wojciech J Grzesik, Tanya C Burch, Michele L Semeraro, Tayab Waseem, Ivan C Gerling, Raghavendra G Mirmira, Margaret A Morris, Jerry L Nadler
Type 1 diabetes (T1D) is a chronic inflammatory disease that is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. The goal of this study was to identify novel protein signatures that distinguish Islets from patients with T1D, patients who are autoantibody positive without symptoms of diabetes, and from individuals with no evidence of disease. High resolution high mass accuracy label free quantitative mass spectrometry analysis was applied to islets isolated by laser capture microdissection from disease stratified human pancreata from the Network for Pancreatic Organ Donors with Diabetes (nPOD), these included donors without diabetes, donors with T1D-associated autoantibodies in the absence of diabetes, and donors with T1D...
2017: PloS One
https://www.readbyqxmd.com/read/28874533/type-1-diabetes-induction-in-humanized-mice
#13
Shulian Tan, Yang Li, Jinxing Xia, Chun-Hui Jin, Zheng Hu, Gaby Duinkerken, Yuying Li, Mohsen Khosravi Maharlooei, Estefania Chavez, Grace Nauman, Nichole Danzl, Maki Nakayama, Bart O Roep, Megan Sykes, Yong-Guang Yang
There is an urgent and unmet need for humanized in vivo models of type 1 diabetes to study immunopathogenesis and immunotherapy, and in particular antigen-specific therapy. Transfer of patient blood lymphocytes to immunodeficient mice is associated with xenogeneic graft-versus-host reactivity that complicates assessment of autoimmunity. Improved models could identify which human T cells initiate and participate in beta-cell destruction and help define critical target islet autoantigens. We used humanized mice (hu-mice) containing robust human immune repertoires lacking xenogeneic graft-versus-host reactivity to address this question...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28870031/-the-clinical-characteristics-of-346-patients-with-igg4-related-disease
#14
P P Zhang, J Z Zhao, M Wang, R E Feng, X W Liu, X M Lai, X J Li, J G Zeng, H J Shi, H D Zhu, W Xue, H Zhang, Y Y Chen, L Y Fei, X F Peng, F C Zeng, Y M Zhang, W Zhang
Objective: To analyze the clinical characteristics of IgG4-related disease (IgG4-RD)so as to improve the understanding of IgG4-RD in China. Methods: IgG4-RD patients were recruited from Peking Union Medical College Hospital between January 2011 and January 2016. All patients were followed-up for more than 6 months. The demographic characteristics, symptoms, organ involvements, laboratory examinations and treatment efficacy were evaluated and analyzed. Results: A total of 346 patients were finally enrolled, including 230 males (66...
September 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28868649/microscopic-findings-in-eus-guided-fine-needle-sharkcore-biopsies-with-type-1-and-type-2-autoimmune-pancreatitis
#15
Sönke Detlefsen, Maiken Thyregod Joergensen, Michael Bau Mortensen
The International Consensus Diagnostic Criteria (ICDC) for the diagnosis of autoimmune pancreatitis (AIP) include the histological criterion that is based on either pancreatic core needle biopsies (CNBs) or surgical specimens. However, CNBs are difficult to obtain by endoscopic ultrasound (EUS). EUS fine-needle aspiration (EUS-FNA) cytology is usually not sufficient for the diagnosis of AIP, but may sometimes contain tissue microfragments. Another approach is EUS-guided histological fine-needle biopsy (EUS-FNB), using needles such as the SharkCore or ProCore needle...
September 3, 2017: Pathology International
https://www.readbyqxmd.com/read/28864875/deciphering-the-pathogenesis-of-human-type-1-diabetes-t1d-by-interrogating-t-cells-from-the-scene-of-the-crime
#16
REVIEW
Sally C Kent, Stuart I Mannering, Aaron W Michels, Jenny Aurielle B Babon
PURPOSE OF REVIEW: Autoimmune-mediated destruction of insulin-producing β-cells within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable. Previously, our understanding of the β-cell specific T cell repertoire was based on studies of autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D; more recently, investigations have included immunohistochemical analysis of some T cell specificities in the pancreas from organ donors with T1D...
September 2, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28851763/the-innate-immune-receptor-mda5-limits-rotavirus-infection-but-promotes-cell-death-and-pancreatic%C3%A2-inflammation
#17
Yu Dou, Howard Ch Yim, Carl D Kirkwood, Bryan Rg Williams, Anthony J Sadler
Melanoma differentiation-associated protein 5 (MDA5) mediates the innate immune response to viral infection. Polymorphisms in IFIH1, the gene coding for MDA5, correlate with the risk of developing type 1 diabetes (T1D). Here, we demonstrate that MDA5 is crucial for the immune response to enteric rotavirus infection, a proposed etiological agent for T1D. MDA5 variants encoded by minor IFIH1 alleles associated with lower T1D risk exhibit reduced activity against rotavirus infection. We find that MDA5 activity limits rotavirus infection not only through the induction of antiviral interferons and pro-inflammatory cytokines, but also by promoting cell death...
September 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28842855/diagnosis-and-management-of-autoimmune-pancreatitis
#18
REVIEW
Phil A Hart, Somashekar G Krishna, Kazuichi Okazaki
Although autoimmune pancreatitis is a relatively uncommon pancreatic disorder, it is an important consideration in the differential diagnosis of jaundice and pancreatic masses to avoid unnecessary surgical resection. The clinical diagnosis of autoimmune pancreatitis involves considering multiple pieces of information including the pancreatic imaging, serum IgG4 level, presence of characteristic other involvement, and histologic findings. Unlike other pancreatic disorders, this condition rapidly responds to treatment with steroids...
August 25, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28842400/increased-effector-memory-insulin-specific-cd4-t-cells-correlate-with-insulin-autoantibodies-in-recent-onset-type-1-diabetic-patients
#19
Justin A Spanier, Nathanael L Sahli, Joseph C Wilson, Tijana Martinov, Thamotharampillai Dileepan, Adam L Burrack, Erik B Finger, Bruce R Blazar, Aaron W Michels, Antoinette Moran, Marc K Jenkins, Brian T Fife
Type 1 diabetes (T1D) results from T-cell mediated destruction of insulin producing beta cells. Insulin represents a key self-antigen in disease pathogenesis as recent studies identified proinsulin responding T-cells from inflamed pancreatic islets of recent onset T1D organ donors. These cells respond to an insulin B chain epitope presented by human leukocyte antigen (HLA) DQ8 molecule associated with high T1D risk. It is now critical to understand insulin specific T-cell frequency and phenotype in peripheral blood...
August 25, 2017: Diabetes
https://www.readbyqxmd.com/read/28839093/imaging-the-emergence-and-natural-progression-of-spontaneous-autoimmune-diabetes
#20
James F Mohan, Rainer H Kohler, Jonathan A Hill, Ralph Weissleder, Diane Mathis, Christophe Benoist
Type 1 diabetes in the nonobese diabetic mouse stems from an infiltration of the pancreatic islets by a mixed population of immunocytes, which results in the impairment and eventual destruction of insulin-producing β-cells. Little is known about the dynamics of lymphocyte movement in the pancreas during disease progression. Using advanced intravital imaging approaches and newly created reporter mice (Flt3-BFP2, Mertk-GFP-DTR, Cd4-tdTomato, Cd8a-tdTomato), we show that the autoimmune process initiates first with a T cell infiltration into the islets, where they have restricted mobility but reside and are activated in apposition to CX3CR1(+) macrophages...
September 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
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